兽研1. 引言
伴侣动物的胃肠道微生物组是一个在代谢和免疫方面具有活性的生态系统，参与营养加工、黏膜屏障完整性、定植抵抗、胆汁酸转化和免疫发育[1,2,3,4,5,6]。在犬和猫中，该生态系统的破坏——通常描述为菌群失调——与慢性胃肠道肠病、抗生素相关性腹泻以及某些肠外疾病相关[2,7]。菌群失调不仅是组成异常，也是一种功能紊乱，其特征为短链脂肪酸产生改变、胆汁酸代谢受损、定植抵抗降低以及兼性病原体扩增[2,8,9,10,11]。慢性胃肠道疾病是兽医门诊和转诊的常见原因。在犬中，近期ACVIM认可的建议倾向于使用慢性炎症性肠病（CIE）这一术语而非炎症性肠病（IBD），因为犬CIE不被认为直接等同于人类IBD[12]。然而，慢性肠病（CE）是一个更广泛的临床术语，涵盖具有持续或反复胃肠道症状的犬，包括可能无法获得肠道活检和炎症组织病理学确认的群体。由于本文综述的犬FMT文献既包括组织病理学确认的炎症性肠病，也包括更广泛的慢性肠病群体，我们在临床证据综合中全程使用CE作为总括术语。CIE保留用于组织病理学支持的炎症性肠病、当前共识指南特别定义的术语，或明确描述为CIE的研究群体。IBD仅在反映原始发表文献中使用的术语或已建立的疾病活动指数时保留。
犬慢性肠病由异质性、多因素疾病表型组成，涉及饮食、肠道微生物群、黏膜免疫、环境因素和宿主易感性之间的相互作用。犬慢性肠病传统上根据治疗反应分为食物反应性肠病（FRE）、抗生素反应性肠病（ARE）、免疫抑制剂反应性肠病（IRE）和无反应性肠病（NRE）。然而，近期进展对这一框架提出了挑战。特别是，一项 refined 分类提出用微生物群相关调节反应性肠病（MrMRE）替代ARE，反映了对经验性抗菌治疗的依赖减少以及对微生物群导向方法的日益使用，包括益生元、益生菌、后生元、饮食调节和粪菌移植（FMT）[13]。更近期的ACVIM认可指南继续强调根据治疗反应进行表型分型，包括食物反应性CIE（CIE-FR）和免疫抑制剂反应性CIE（CIE-IR）[12]。尽管在饮食、微生物群导向或免疫调节干预后临床症状可能改善，但潜在的微生物和代谢异常可能持续存在[2,8,14,15,16,17,18,19]。在猫中，慢性肠病（CE）仍是更广泛的临床术语，炎症性慢性肠病与小肠细胞淋巴瘤之间的诊断重叠造成了额外的复杂性[20,21]。FMT涉及将来自健康、经过筛查的供体的处理粪便材料转移给患病受体。在人类医学中，FMT最成熟的应用是复发性艰难梭菌感染[22,23,24,25,26,27,28]，在炎症性肠病（包括溃疡性结肠炎）和代谢性疾病中也有额外但更多变的证据[29,30,31,32,33,34,35,36,37,38]。然而，FMT在兽医医学中的应用需要谨慎，因为犬和猫在饮食、胃肠道解剖、胆汁酸谱、核心微生物类群、病原体风险和监管背景方面与人类不同。因此，兽医FMT应基于物种特异性临床证据进行评估，而非直接从人类研究外推[2,39]。
对伴侣动物进行FMT的兴趣日益增加，因为该干预针对的是作为生态系统的肠道微生物群落，而非单一病原体或分离的益生菌菌株。潜在的治疗效应包括供体微生物定植、致病共生菌抑制、微生物代谢物恢复、上皮屏障功能改善、免疫调节以及通过肠-皮肤轴和肠-脑轴的全身性信号传导[39,40,41,42,43,44,45,46,47,48,49]。然而，大多数兽医研究仍然规模较小、缺乏对照或设计异质性大，且解读进一步受到以下因素的限制：同时进行的治疗、缺乏盲法、部分研究依赖主观或主人报告的结果、随访不完整，以及供体选择、FMT制备、给药途径、剂量和治疗频率的显著差异。这些因素使得难以将临床改善具体归因于FMT。FMT可能通过微生物群落重构、定植抵抗、代谢恢复、屏障和免疫调节以及肠外肠-皮肤或肠-脑信号传导影响受体健康。这些途径的证据强度因物种、适应症、制剂、给药途径和研究设计而异，因此不应被视为同等确立的机制。这些提出的机制及其不同程度的证据支持总结于图1。
[图：犬猫粪菌移植（FMT）的拟定机制与证据框架。]
以往关于伴侣动物FMT的综述通常受限于物种、临床适应症或对微生物组机制的侧重，鲜有将近期临床证据与治疗给药、制备、安全性和标准化方面的进展相结合。重要的是，兽医FMT文献也随时间发生了显著演变。早期证据以个体病例报告、小型病例系列和以直肠给药为主，而近期研究越来越多地包括前瞻性队列、随机或对照试验、重复治疗方案和口服冻干制剂。结局评估同样从以临床观察为主扩展到包括经验证的疾病活动指数、菌群失调指标、微生物组分析和供体-受体微生物定植。近期研究还拓宽了所研究的适应症范围，同时提供了关于耐受性、供体筛查和治疗标准化的更系统信息。因此，本综述不仅综合了犬和猫FMT的当前证据，还考察了该领域在临床适应症、给药途径和制剂、治疗方案、临床和微生物组相关反应、不良反应和方法学严谨性方面的演变。通过明确区分对照与非对照证据并识别临床应用和研究设计中的变化，我们旨在阐明哪些进展可能已与临床决策相关，哪些应主要指导未来研究。因此，本综述的主要贡献是提供了一个跨物种、时间情境化的框架，将临床结局、机制合理性、产品标准化和安全性考量联系起来。
2. 材料与方法
2.1. 综述设计与范围
本文设计为伴侣动物FMT的结构化叙述性综述，主要侧重于犬和猫。本综述旨在综合临床相关证据，同时整合解读兽医FMT领域所需的选定机制、方法学 and 安全性文献。由于现有研究在设计、适应症、给药途径、给药方案和结局指标方面差异显著，进行荟萃分析并不合适。本综述未注册为系统综述方案，也未包括正式偏倚风险评估。
符合条件的出版物包括涉及犬、猫或伴侣动物背景下FMT的同行评审原始研究、对照试验、队列研究、病例系列、病例报告、微生物组或代谢组学研究、安全性报告、临床指南、制备方案和相关综述。仅专注于家畜、实验动物或野生动物的研究被排除，除非其提供了与伴侣动物FMT直接相关的方法学或安全性信息。无完整同行评审稿的会议摘要以及仅限于益生菌、益生元、抗生素或饮食而无FMT的研究被排除在核心FMT证据综合之外，但选定的非FMT微生物组干预措施作为比较背景进行了讨论。
2.2. 文献检索与证据综合
通过结构化检索PubMed/MEDLINE、PubMed Central和Web of Science数据库，识别2005年1月至2026年5月发表的文献，最终检索于2026年5月进行。检索词将FMT相关术语与物种及疾病术语相结合，包括“fecal microbiota transplantation”“faecal microbiota transplantation”“fecal microbial transplantation”“faecal microbial transplantation”“FMT”“fecal transplant”“stool transplant”“dog”“canine”“cat”“feline”“companion animal”“chronic enteropathy”“chronic inflammatory enteropathy”“protein-losing enteropathy”“dysbiosis”“diarrhea”和“donor screening”。根据各平台的索引和检索功能调整数据库特定语法，同时在所有数据库中保留相同的核心概念和纳入排除框架。基于以下核心概念为每个平台制定数据库特定检索策略：（“fecal microbiota transplantation” OR “faecal microbiota transplantation” OR FMT OR “fecal transplant” OR “stool transplant”）AND（dog OR canine OR cat OR feline OR “companion animal”）AND（enteropathy OR diarrhea OR dysbiosis OR “donor screening” OR safety）。手动筛选关键综述、临床研究和伴侣动物FMT指南的参考文献列表，以识别其他相关文献。核心临床证据综合纳入22篇选定的伴侣动物FMT临床报告或研究，包括17项犬类和5项猫类研究。在涉及特定应用、给药途径或方法学考量时，对其他临床报告进行了讨论。
筛选、研究选择和数据提取由作者完成。纳入的研究为经过同行评审的原创临床报告，描述了在预定发表期间内对犬或猫实施FMT的情况。无完整同行评审稿件的会议摘要、不涉及FMT的研究以及非临床综述或方法学论文被排除在核心临床研究计数之外。纳入资格不以研究结局、样本量、给药途径或报告完整性为依据。对于纳入的研究，在有所报告的情况下提取物种、适应证、研究设计、FMT制备与途径、临床和微生物组结局、不良事件、随访及主要局限性。根据研究设计、有无对照组、样本量、随访持续时间、客观微生物组或代谢组学终点以及同期治疗所致混杂的易感性，对证据进行描述性分类。本综述全程使用以下叙述性证据类别：对照性兽医临床证据、非对照性兽医临床证据、机制性兽医证据以及外推性或假设生成性证据。未应用正式偏倚风险评估工具或GRADE评估；因此，正文和表格中的证据标签应解释为描述性证据类别，而非正式的证据确定性评级。
3. 伴侣动物肠道微生物组：健康、菌群失调与诊断评估
3.1. 健康犬和猫的微生物组
粪便样本的非培养依赖性测序显示，健康犬表现出多种粪便微生物谱，通常以厚壁菌门、梭杆菌门、拟杆菌门、变形菌门和放线菌门为特征[50,51]。梭杆菌属是物种特异性解读的一个典型例子：在犬中，它通常在健康粪便群落中丰度较高，可能参与蛋白质和氨基酸发酵，而在人类中，某些梭杆菌属物种更多在疾病背景下被讨论[2,50]。大规模犬类测序研究细化了核心分类群的物种水平定义，并强调了饮食、年龄和品种对微生物结构的影响[52,53,54]。重要的是，不应假设粪便微生物谱能完全代表黏膜相关或更近端肠道的群落。
猫与犬共享一些优势细菌门，但在微生物比例和代谢背景方面存在差异，这与其专性肉食性一致[1,55,56]。这些差异具有临床重要性，因为供体筛查、供体-受体匹配和结局解读应具有物种特异性。被认为对猫健康的供体特征不应被假定能恢复健康的犬类微生物组，反之亦然。
3.2. 菌群失调及其功能后果
患有慢性炎症性肠病（CIE）的犬通常表现为变形菌门（包括大肠杆菌）扩增、梭杆菌门减少，以及梭菌纲XIVa和IV簇内厚壁菌门分类群的减少[57,58,59]。然而，大肠杆菌相对丰度的增加不应被解释为致病性的证据，因为常用的16S rRNA测序和宽泛的qPCR方法通常无法可靠地区分共生菌株与致病菌株。这些组成变化伴随着功能紊乱，包括粪便中乙酸盐、丙酸盐和总短链脂肪酸浓度降低，以及部分由于希拉诺梭菌耗竭导致的胆汁酸转化改变[8,9]。然而，粪便短链脂肪酸浓度并不直接反映肠道产生量，因为它们还受宿主吸收、微生物利用、肠道传输、饮食和粪便含水量的影响。因此，短链脂肪酸可利用性的改变可能促进上皮和免疫稳态受损，尽管仅凭粪便浓度无法确定肠道产生减少[8,60,61,62,63,64]。
猫的菌群失调特征研究较少，但患有慢性肠病（尤其是炎症表型）或小细胞性肠道淋巴瘤的猫表现出可能具有诊断和预后相关性的微生物模式[20,21,65,66,67]。抗生素相关性菌群失调在伴侣动物中也具有临床意义。甲硝唑可在治疗期后破坏微生物组组成和代谢谱，这为旨在恢复微生物功能而非仅仅缓解腹泻的干预措施提供了依据[68,69]。
3.3. 菌群失调指数作为临床和研究工具
基于qPCR的菌群失调指数（DI）提供了一种实用的总结性指标，用于评估与粪便菌群失调相关的预定义细菌 panel 的变化。它不能涵盖整个肠道微生物组或所有形式的菌群失调，因此应被解释为补充性而非全面性的微生物组指标。在犬中，DI使用选定的细菌靶标和总细菌丰度，已显示出区分CIE犬与健康犬的诊断效用[70]。DI已成为犬FMT研究中常见的终点指标，并可能有助于识别更可能应答的患者；多项研究表明基线菌群失调严重程度与治疗结果相关[71,72]。猫DI也已被开发，并越来越多地用于猫微生物组研究[73]。
这些工具之所以有价值，是因为它们提供了超越主人报告临床症状的客观终点。然而，DI结果应结合临床活动评分、饮食、用药史、抗菌药物暴露和疾病表型进行解读。犬和猫粪便微生物组共享几个优势细菌门，但在微生物比例和代谢背景上存在差异，支持对供体特征和FMT结果进行物种特异性解读。菌群失调可能涉及细菌组成的变化，同时伴有短链脂肪酸浓度、胆汁酸转化、上皮屏障功能和免疫调节的改变。这些关系总结于图2。
[图：犬种特异性健康肠道微生物组、菌群失调相关功能紊乱及诊断评估]
4. 犬医学中的FMT
犬FMT证据已从孤立病例报告扩展到前瞻性队列、多中心研究和小型随机试验。表1总结了选定的临床研究，并标明研究设计作为实用的证据水平标志。总体而言，临床文献在犬慢性肠病（CE）方面最为成熟，尽管纳入人群在诊断特征上存在差异，且并非所有研究都要求或可获得肠道炎症的组织病理学确认。大多数现有证据仍为观察性、非对照或把握度不足，对照性发现仍然有限且异质性较大。最强的对照证据来自选定的急性感染性情况，尤其是犬细小病毒性肠炎，而其他急性腹泻综合征的证据仍不一致。
Table 1. Summary of selected canine FMT clinical studies, with study design reported descriptively.
| Study | Design | n | Indication | Route | Key Outcome |
|---|---|---|---|---|---|
| Pereira et al. [ 74 ] | RCT | 66 | Canine parvovirus enteritis | Enema | Faster diarrhea resolution; shorter hospitalization |
| Niina et al. [ 75 ] | Case report | 1 | Refractory CE (histopathologically confirmed CIE; reported as IBD in the original study) | Repeated enema | CIBDAI improved from 9 to 4; Proteobacteria decreased |
| Chaitman et al. [ 76 ] | Prospective treatment trial | 18 | Acute diarrhea | Enema | DI decreased after FMT, whereas dysbiosis persisted after metronidazole at day 28 |
| Niina et al. [ 77 ] | Uncontrolled clinical study | 9 (16S sequencing in 3) | CE (histopathologically confirmed CIE; reported as IBD in the original study) | Single rectal enema | CIBDAI decreased and Fusobacterium increased after FMT |
| Gal et al. [ 78 ] | Pilot study | 8 | AHDS | Enema | No additional benefit over standard care |
| Collier et al. [ 79 ] | Double-blind randomized clinical trial | 13 (7 FMT; 6 placebo) | CE (histopathologically confirmed CIE; reported as IBD in the original study) | Single retention enema | CCECAI decreased over time in both groups; no significant between-group difference |
| Cerquetella et al. [ 80 ] | Case report | 1 | Relapsing diarrhea | Oral capsules | Clinical improvement with no serious relapses during 18-month follow-up; maintenance prednisolone was continued |
| Toresson et al. [ 71 ] | Retrospective case series | 41 | CE | Enema | 31/41 dogs improved; lower baseline DI was associated with better response |
| Sugita et al. [ 81 ] | Uncontrolled trial | 12 | Atopic dermatitis | Single oral administration | CADESI-04 improved; exploratory extra-intestinal signal |
| Brugnoli et al. [ 82 ] | Prospective multicenter cohort | 171 enrolled; 111 analyzed | CE | Oral lyophilized capsules | 82% response among analyzed dogs; missing outcome data and absence of a control group limit inference |
| Hanifeh et al. [ 83 ] | Double-blind RCT | 13/14 analyzed | Tylosin-responsive enteropathy | Oral capsules | 71.4% non-relapse after FMT vs. 50% after placebo; difference not statistically significant |
| Rojas et al. [ 84 ] | Cohort | 54 | Chronic gastrointestinal signs | Oral capsules | 18% donor–recipient ASV sharing; Butyricicoccus increased |
| Pérez-Accino et al. [ 85 ] | Prospective uncontrolled study | 7 | CE (histopathologically confirmed CIE) | Rectal FMT | Clinical severity decreased after FMT; improvement was not accompanied by consistent longitudinal changes in fecal microbial community composition or diversity |
| Vecchiato et al. [ 86 ] | Prospective multicenter | 20 | Diet-refractory CE | Enema | Median CIBDAI improved from 5 to 1; 17/20 improved at 3 months |
| Toresson et al. [ 72 ] | Prospective longitudinal | 39 | Refractory CE | Repeated enemas | 28/39 responded; corticosteroid dose reduced in 13 dogs |
| Schreiber et al. [ 87 ] | Case report | 1 | Protein-losing enteropathy with concurrent protein-losing nephropathy | Repeated enema and oral lyophilized FMT | Repeated FMT was associated with improvement in clinical status, body weight, serum albumin, fecal consistency, and DI; repeated treatment was required to maintain the response |
| Allerton et al. [ 88 ] | Blinded randomized controlled trial | 42 (25 FMT; 17 control) | CE | Single retention enema | No significant additional clinical benefit of FMT plus dietary management over dietary management alone for owner-reported improvement, CIBDAI, or fecal score |
4.1. 慢性肠病及相关表型
犬FMT研究最广泛的适应症是慢性肠病（CE），尽管各研究间的诊断流程和组织病理学确诊的可获得性存在差异。回顾性和前瞻性研究报告FMT后CIBDAI或相关疾病活动评分降低，尤其是在涉及反复给药的方案中[71,72,86]。Toresson等报告41只接受辅助灌肠FMT的CE犬中31只临床改善，并确定基线菌群失调指数（DI）较低是反应的潜在预测因素[71]。Vecchiato等随后在一项前瞻性多中心研究中报告20只饮食难治性CE犬中17只临床改善，CIBDAI中位数从5降至1[86]。在一项难治性CE犬的前瞻性纵向研究中，反复FMT与39只犬中28只的临床反应相关，并在部分病例中减少了皮质类固醇使用[72]。微生物组相关终点，包括DI变化、细菌丰度或供体-受体ASV共享，应与临床结局分开解读，其本身不能证明临床疗效。
口服冻干胶囊可通过实现反复门诊给药来提高实用性。Brugnoli等报告，在初始前瞻性多中心队列的171只犬中，111只可分析的接受口服冻干FMT胶囊治疗的CE犬中82%出现阳性临床反应[82]。该结果在临床上令人鼓舞，但非对照设计、大量治疗后数据缺失以及缺乏安慰剂对照意味着因果解读仍应谨慎。
随机对照证据仍然有限。Collier等将13只经组织病理学确诊为慢性炎症性肠病（CIE，原文发表时报告为IBD）的犬随机分配至FMT组或安慰剂组，均在标准治疗基础上加用。两组的CCECAI均随时间下降，FMT组数值上降幅更大，但未检测到显著的组间差异[79]。Hanifeh等在泰勒菌素反应性肠病犬（沿用原研究的治疗反应术语）中提供了双盲概念验证证据，报告口服FMT胶囊后复发少于安慰剂，尽管样本量较小[83]。
综上所述，现有犬类数据支持进一步研究FMT作为微生物组导向的辅助治疗，但尚未确立明确的临床疗效。大多数阳性发现来自观察性研究或小型研究，且由于方案异质性、合并治疗及对照重复有限，因果解释仍然受限。在FMT可被推荐为犬慢性肠病的常规治疗之前，需要开展更大规模的假对照试验，采用标准化的供体筛查、剂量探索、受控的背景治疗、客观的微生物组终点以及无复发生存结局。
4.2. 急性腹泻、细小病毒与急性出血性腹泻综合征
急性胃肠道疾病中最有力的犬类对照证据来自犬细小病毒性肠炎。在一项纳入66只幼犬的随机对照试验中，与单纯标准治疗相比，灌肠式FMT加速了腹泻缓解并缩短了住院时间[74]。这一发现具有临床重要性，因为其在高发病率传染病背景下采用了有意义的临床终点。
在非特异性急性腹泻中，一项比较FMT与甲硝唑的前瞻性非随机治疗试验发现，两组的临床症状均改善，而FMT后微生物组恢复更为明显[76]。这一区别凸显了症状缓解与微生物组恢复之间的差异。相反，一项在急性出血性腹泻综合征中开展的初步研究发现，单次灌肠式FMT较标准支持治疗无额外获益[78]。这些混合结果提示，时机、疾病机制、剂量、频率及给药途径可能强烈影响急性胃肠道疾病的结局。
4.3. 肠外应用
早期研究已探索FMT在胃肠道疾病之外的应用。Sugita等报告，在特应性皮炎犬中单次口服FMT后CADESI-04评分改善[81]；Watanangura等报告，在耐药性癫痫犬中行为共病及尿液神经递质谱发生变化[89]。这些发现属于假设生成性而非改变实践，但与肠-皮肤轴和肠-脑轴信号传导的更广泛概念一致[2,45]。
肠外应用目前应视为探索性。未来研究应包括随机对照、经过验证的皮肤病学或神经学终点、合并用药控制、代谢组学评估及纵向微生物组分析，以确定临床变化是否可重复并与FMT存在机制关联。
4.4. 口服冻干FMT作为实用性进展
新鲜或冷冻灌肠式FMT可将高微生物剂量直接递送至远端肠道，但通常需要保定、镇静、即时产品处理或转诊中心基础设施。口服冻干胶囊解决了若干实际限制，允许在兽医监督下重复门诊或由主人给药、更易储存及批次水平质量控制。初步研究支持其在犬中的可行性和耐受性[90]，基于胶囊的研究已证明可检测到供体微生物信号[83,84]。未解决的关键问题包括最佳剂量、治疗持续时间、胶囊活力、供体选择、定植一致性，以及经上消化道通过是否较直肠给药改变疗效。
5. 猫医学中的FMT
猫FMT研究仍然非常有限，临床研究少且对照证据有限。现有研究受限于样本量小、适应症异质、设计缺乏对照、部分研究采用主观或主人报告的结局以及随访不完整。尽管已报告FMT后微生物组变化，但这些发现不应被解释为治疗获益的证据，临床疗效尚未确立。表2总结了部分猫类报告和试验，并区分了对照与非对照证据。
Table 2. Summary of selected feline FMT studies, with study design reported descriptively.
| Study | Design | n | Indication | Route | Key Outcome |
|---|---|---|---|---|---|
| Furmanski and Mor [ 91 ] | Case report | 1 | Refractory ulcerative colitis | Enema | Sustained remission reported for 11 months |
| Rojas et al. [ 92 ] | Observational microbiome cohort | 46 | Chronic digestive signs | Oral capsules | ~13% donor–recipient ASV sharing; microbiome shifted toward healthy reference profiles in some cats |
| Karra et al. [ 93 ] | Prospective blinded controlled trial | 28 | Chronic enteropathy | Single enema | Well tolerated; no significant DI or FCEAI improvement versus controls |
| Lee et al. [ 94 ] | Retrospective case series | 9 | CE or therapy-resistant diarrhea | Repeated rectal enemas | Predominantly grade I–II AEs; one grade III severe abdominal pain event; 8/9 cats showed complete or partial clinical response |
| Martini et al. [ 95 ] | Randomized experimental study | 25 | Metronidazole-induced dysbiosis in healthy adult cats | Oral FMT capsules plus diet | FMT was the only intervention to normalize DI, although the effect was transient in some cats |
5.1. 慢性肠病与慢性消化系统症状
首例有文献记载的猫病例报告描述了一只患有难治性溃疡性结肠炎的猫在两次灌肠FMT操作后获得持续缓解[91]。更大规模的经验来自对患有慢性呕吐、腹泻或便秘的猫进行的口服胶囊研究。Rojas等报告了46只患有慢性消化系统症状的猫的微生物组水平变化，包括供体-受体共享ASV以及部分动物向更健康的参考谱偏移[92]。由于该研究为无对照研究且主要关注微生物组结局，这些发现不应被解释为临床疗效的证据。
首项前瞻性、盲法、对照的猫慢性肠病试验显示，与对照治疗相比，单次灌肠FMT后菌群失调指数（DI）或猫慢性肠病活动指数（FCEAI）均无显著改善[93]。这一阴性对照结果很重要，因为它防止了对无对照猫病例报告和观察性队列的过度解读。FCEAI提供了相关的临床活动度指标[96]，而猫炎症性肠病与低级别肿瘤性肠病之间的诊断重叠仍是一个重要的解释挑战[97]。FMT中性结果的可能的解释包括样本量不足、单次给药暴露、仅灌肠给药、两组均同时接受标准治疗以及猫慢性肠病表型之间的异质性。因此，未来的猫试验应在提出疗效声明之前评估重复给药、口服与直肠给药、表型分层以及更长时间的随访。
因此，当前的猫证据应被解释为支持生物学活性和短期耐受性，而非已确立的临床疗效。仅有微生物组变化不应被视为治疗获益的证据，现有证据不足以确定长期安全性。在获得重复给药、假对照、表型分层且随访时间更长的试验之前，猫的常规临床使用应保持谨慎，最好以产生证据为目的。
5.2. 抗生素相关性菌群失调的实验性恢复
一项在25只接受甲硝唑治疗的健康成年猫中进行的随机实验研究发现，FMT是唯一在干预后即刻使猫菌群失调指数（DI）正常化的干预措施，尽管该效应在部分猫中似乎为一过性[95]。由于该研究使用的是健康猫中实验性诱导的抗生素相关性菌群失调，而非自然发生的慢性肠病，其发现支持FMT的微生物组水平生物学效应，但不应被解释为对患有慢性肠病的猫具有临床疗效的证据。未来的临床研究应评估重复给药、口服与直肠给药、疾病表型分层以及停用抗菌药物后的长期随访。
5.3. 猫的安全性与供体筛查
可获得的猫安全性数据有限。Lee等报告了9只猫灌肠FMT后主要发生I-II级不良事件，其中1例III级事件涉及严重腹痛；大多数不良事件经支持性治疗或无干预后缓解[94]。对照性猫慢性肠病试验也报告了耐受性良好且无严重不良事件[93]。猫供体筛查在若干方面应比犬筛查更严格，包括除细菌病原体、寄生虫和抗菌药物耐药微生物外，还应检测猫免疫缺陷病毒、猫白血病病毒和胎儿三毛滴虫[98]。
6. 制备、标准化与临床指南
6.1. 供体筛查与安全保障
供体筛查是FMT安全性的关键组成部分，但安全的临床使用还取决于适当的受体制选择、标准化处理、批次质量控制和可追溯性、适当的给药方式以及系统性的不良事件监测。伴侣动物FMT指南建议筛查肠道细菌病原体，如沙门菌、弯曲杆菌、艰难梭菌、产气荚膜梭菌和产超广谱β-内酰胺酶大肠杆菌；寄生虫如贾第虫和隐孢子虫；以及相关情况下的物种特异性病毒或原虫病原体[98,99,100]。基于培养的筛查、靶向分子检测和更广泛的耐药组分析提供互补但非等价的信息；因此，选择性培养阴性并不能排除所有耐药微生物或抗菌药物耐药基因。供体项目应确定最低筛查组合、定期复筛间隔、排除标准以及阳性结果的处理程序，包括暂时或永久排除供体以及在进一步使用前重新评估。供体还应临床健康、近期无抗菌药物暴露并维持稳定饮食。
未来的临床方案至少应报告供体健康标准、近期抗菌药物暴露、饮食稳定性、筛查组合、复筛间隔、粪便处理时间、储存条件、批次标识、受体监测和不良事件分级。对于猫，供体项目除采用伴侣动物通用的肠道病原体和抗菌药物耐药防护措施外，还应明确包括猫特异性传染病筛查。
由于FMT转移的是一种复杂且特征不完全明确的生物制品，病原体检测阴性无法消除所有风险。因此，安全项目应包括供体复筛间隔、批次可追溯性、受体监测、不良事件报告以及在可行情况下的抗菌药物耐药基因监测。
6.2. 新鲜、冷冻和冻干制剂
微生物DNA丰度不一定反映活微生物载量，总体活力的保存仍可能伴随敏感分类群的选择性丢失。因此，微生物活力和产品标准化不仅取决于制剂是新鲜、冷冻还是冻干，还取决于处理条件、储存、氧气暴露和产品特异性验证。新鲜制剂可能最大限度保持活力，但需要快速处理和给药。冷冻制剂提高了安排灵活性，但需要经验证的冷冻保护剂和冷链储存。冻干制剂提供最大的实际标准化程度并支持口服胶囊给药，但活力、剂量等效性、定植一致性和长期稳定性需要持续验证[101]。新鲜、冷冻和冻干FMT制剂之间的实际差异总结于表3。
Table 3. Practical comparison of FMT preparation methods for companion animals and their likely clinical-use scenarios.
| Parameter | Fresh | Frozen | Lyophilized |
|---|---|---|---|
| Viability | Generally highest immediately after processing | High if cryoprotectant and storage are optimized | Good when validated; product-specific |
| Storage | Hours; immediate use preferred | Usually ultra-low temperature storage | Room temperature or refrigerated storage may be possible depending on product |
| Convenience | Low; same-day preparation | Moderate; cold chain required | High; capsules and batch production possible |
| Standardization | Difficult | Moderate | Highest potential |
| Main limitation | Logistics and donor availability | Storage and thawing effects | Dose equivalence, viability, and regulatory classification |
6.3. FMT的直肠/灌肠给药
直肠或灌肠给药是兽医学中FMT常用给药途径之一，已应用于犬和猫。除上述研究外，Ural等报告了以直肠FMT为主治疗患有各种疾病状况的犬的大量临床经验[102]，而直肠FMT也已在共济失调猫中进行了研究[103]。这些研究提供了关于直肠FMT可行性的额外临床经验，尽管需要进一步对照研究以确定其在不同适应症中的疗效。
6.4. 监管和商业标准化
该领域正从逐例临床制备转向标准化方案和商业胶囊产品。这一转变可能改善可重复性、质量控制、可及性和治疗依从性，但也提出了重要的监管问题。兽医FMT产品尚未有明确协调的监管路径，其作为生物制品、兽药产品、补充剂或配制制剂的分类仍取决于具体情况。在更广泛的临床采用之前，需要明确的产品分类、最低供体筛查要求、批次放行标准、标签标准、不良事件报告系统和抗菌药物耐药监测[98,101,104]。
7. 作用机制
FMT 不太可能通过单一机制发挥作用。多层面模型更为合理：供体微生物可能部分定植，受体微生物群落可能被重构，微生物代谢功能可能恢复，屏障和免疫功能可能改善，全身信号传导可能影响肠外结局。然而，这些机制的证据基础各不相同。在伴侣动物中，直接支持最强的是可测量的微生物组变化，代谢终点的证据正在涌现，而免疫调节和肠-皮肤或肠-脑信号传导仍主要依赖人类、实验性或产生假设的兽医数据。在伴侣动物中，直接证据最强的是可测量的微生物组变化和供体-受体微生物共享，代谢恢复的证据正在涌现，而免疫介导和肠外效应的证据有限或仅能产生假设。这些相互关联的机制及其不同的证据水平总结于图3。不应假定治疗后微生物组变化来源于供体或在机制上导致了临床改善，尤其是在非对照研究中，饮食、抗菌药物撤除、同时进行的治疗、自发恢复和时间变异也可能起作用。
[图：伴侣动物粪菌移植（FMT）拟定的多层级机制。]
7.1. 微生物定植与群落重构
菌株水平的纵向证据为供体定植提供了最强支持，而仅凭共享ASV不应被视为定植的确认。人类宏基因组研究表明，供体菌株定植因疾病、供体-受体相容性和微生物分类群而异，且较高的定植率可能与更好的结局相关[40]。兽医数据正在涌现：口服FMT研究报告了犬和猫中可测量的供体ASV共享，尽管比例不高[84,92]。共享ASV可能代表多个菌株、低于检测阈值的预先存在的分类群，或更广泛人群中常见的分类群。部分定植不应被忽视，因为生态效应也可能通过短暂定植、交叉喂养、噬菌体转移、代谢物变化和致病共生菌抑制而产生[41]。因此，治疗后群落变化、可证明的供体来源定植以及介导临床改善的微生物组变化应被视为不同的证据水平。
7.2. 代谢恢复
代谢恢复可能与组成变化同样重要。患有CIE的犬表现出粪便短链脂肪酸减少和胆汁酸代谢改变[8,9]。短链脂肪酸产生菌的恢复可能支持结肠细胞能量供应、上皮紧密连接完整性和调节性免疫通路。Clostridium hiranonis或其他胆汁酸转化菌的恢复可能影响初级至次级胆汁酸转化和炎症相关受体信号传导[2,9,48,105,106,107]。然而，物种特异性胆汁酸池和饮食相关发酵模式意味着不能假定犬、猫和人类的机制完全相同。
7.3. 免疫调节与屏障功能
FMT可能通过增加定植抵抗、减少病原体相关抗原刺激、改善上皮屏障功能和促进调节性免疫通路来减少黏膜免疫激活[22,42,43,44,61,108,109,110,111,112]。然而，在犬和猫中，这些免疫学变化介导临床反应的直接证据仍然有限。未来的兽医研究应包括黏膜细胞因子谱分析、调节性T细胞标志物、分泌型免疫球蛋白A、组织病理学、代谢组学和纵向临床终点，以检验免疫学变化是先于临床改善还是仅仅伴随临床改善。
7.4. 肠-皮肤与肠-脑轴信号传导
在特应性皮炎和癫痫中的探索性犬类研究与肠-皮肤和肠-脑轴假说一致[81,89]。候选介质包括微生物代谢物、神经活性化合物、迷走神经信号传导、下丘脑-垂体-肾上腺轴效应和全身免疫调节[2,45,49]。在对照试验重复临床获益并确定反应生物标志物之前，这些应用应被视为机制线索而非已确立的适应证。
8. FMT与其他微生物组调节疗法的比较
8.1. 益生菌与益生元
益生菌和益生元比粪菌移植（FMT）更易于调控、给药和标准化，但其效果通常具有菌株特异性、底物特异性、病症特异性，且往往为一过性[18,113,114,115,116,117]。犬猫的一些益生菌试验报告了对急性腹泻、粪便稠度或特定胃肠道结局的益处，但系统评价普遍将证据等级评定为有限、异质性大或临床相关性不一[113,114,118,119]。益生元可通过选择性提供底物来支持内源性微生物活性，但不能直接替代被破坏的微生物群落。FMT在概念上有所不同，因为它转移的是一个复杂的微生物生态系统，包括多种活菌分类群及相关功能能力，而非一种或少数几种选定微生物或底物。然而，直接比较应谨慎进行，因为益生菌的证据基础包括系统评价和对照试验，而兽医FMT的多数证据仍基于小型或非对照研究。因此，两种方法应采用可比标准进行评估，包括研究质量、效应量、安全性、持久性和临床相关性。
8.2. 后生元、噬菌体疗法和限定性菌群组合
后生元、噬菌体疗法和限定性微生物菌群组合最终可能为全粪便FMT提供更精确和标准化的替代方案[48,110,120,121,122,123,124]。后生元避免了与活微生物转移相关的风险，噬菌体可被设计或筛选以靶向特定细菌病原体，限定性菌群组合可以已知组成和质量控制标准进行生产。全群落FMT的生态复杂性是否比更具靶向性的微生物组方法提供具有临床意义的优势仍不确定。需要进行比较研究以确定哪些患者需要广泛的生态系统层面干预，哪些患者可能对靶向微生物组衍生产品充分应答。
8.3. 实际临床定位
目前，有记录的菌群失调、难治性或复发性胃肠道疾病、抗生素相关性菌群失调，以及对适当饮食或常规治疗应答不完整，应被视为潜在的临床研究背景，而非FMT的已验证适应证。同样，不应假定菌群失调指数的严重程度或正常化能预测或确认临床应答。当有指征时，FMT不应替代诊断性检查、饮食试验、寄生虫控制、抗菌药物管理和免疫抑制治疗。在对照试验之外使用时，临床医生应采用标准化的供体筛查、批次可追溯性、不良事件监测和畜主知情同意，并应将干预措施定位为产生证据的阶段，而非对大多数适应证已明确确立。在临床研究中，菌群失调指数等微生物组终点应与疾病活动评分、药物减量、无复发生存期、不良事件监测和生活质量指标一同解读。
9. 知识空白与未来方向
9.1. 主要证据空白
核心证据空白在于缺乏足够把握度的随机假手术对照试验来评估FMT在犬猫慢性肠病（CE）中的作用。现有研究往往样本量小、非对照、回顾性，或受同时进行的标准治疗混杂[71,72,79,82,88,93]。在犬类研究中，诊断性检查的差异以及肠道炎症组织病理学确认的可及性不一致进一步增加了异质性。这一局限性在猫科医学中尤为重要，因为对照研究和入组动物数量仍然很少。给药和递送方案也 largely 基于经验。已发表研究在新鲜、冷冻或冻干材料的使用；灌肠与口服给药；单次与重复给药；供体选择；基础饮食；合并用药；以及随访持续时间方面存在差异。
长期安全性仍未充分表征。大多数兽医研究报告数天至数月的结果，仅有孤立报告提供更长期随访[80]。关键未解决问题包括供体微生物定植的持久性、复发的时间与预测因素、对抗菌药物耐药基因携带的影响、人畜共患病原体转移的风险，以及免疫功能低下患者或严重肠道炎症动物的安全性。供体动物的福利和伦理管理也值得考虑，特别是当供体合格性可能涉及限制性饲养、饮食控制或反复采集粪便时。
9.2. 研究优先事项
优先事项1：在犬猫CE中开展足够把握度的假手术对照随机试验，采用标准化背景治疗、明确规定的诊断标准、表型分层、在可获得时明确报告组织病理学确认，以及预设的临床有意义终点。
优先事项2：开展头对头给药途径和剂量研究，比较灌肠、口服胶囊和联合方案，同时控制微生物剂量、活力、给药频率和治疗持续时间。
优先级3：整合宏基因组学、代谢组学、胆汁酸谱分析、短链脂肪酸测定、免疫表型分析和经验证的临床活动评分的多组学机制研究。
优先级4：供体优化研究，比较通用供体、混合供体、饮食匹配供体、微生物组定义供体以及病原体和抗菌药物耐药性筛查供体项目，同时考虑供体福利和伦理管理。
优先级5：长期安全性监测，延伸至至少12个月，包括复发、不良事件、抗菌药物耐药性标志物、微生物组持久性以及主人报告的生活质量结局。
9.3 报告标准与同一健康考量
兽医粪菌移植研究应报告供体标准、筛查检测、粪便处理时间、处理方法、储存条件、微生物剂量或经论证的替代指标、可获得的活力数据、给药途径、给药频率、受体饮食、合并用药、不良事件分级以及微生物组终点。动物粪便移植报告GRAFT框架提供了有用的原则，但可能需要针对伴侣动物的扩展[125]。
由于犬和猫与人类密切接触，粪菌移植还具有同一健康维度。供体材料筛查不仅应保护受体，还应减少人畜共患病原体传播和抗菌药物耐药性在家庭和兽医环境中传播的风险[98,104]。因此，负责任的临床转化不仅需要疗效试验，还需要标准化报告、可追溯的供体筛查、长期安全性监测以及针对物种的常规兽医使用指南。
10. 本综述的局限性
本综述采用结构化叙述方法，而非注册系统综述。因此，未进行正式偏倚风险评估、PRISMA流程图、详尽检索产出计数或荟萃分析。因此，综合结果可能受到发表偏倚、选择性报告以及对异质性研究设计、人群、方案和结局指标的叙述性解读的影响。此外，一些近期研究设计为初步性质或随访有限，这限制了对缓解持久性和长期安全性的结论。文献检索仅限于PubMed/MEDLINE、PubMed Central和Web of Science，且未进行独立双人筛选和数据提取，这可能增加了主观研究选择或遗漏相关证据的可能性。此外，在相关情况下使用了有限的非同行评审数据，研究人群、粪菌移植方案、结局指标和随访的巨大异质性进一步限制了研究间的可比性。犬慢性肠病研究之间的诊断特征也存在差异，且肠道炎症的组织病理学确认未一致进行或要求，限制了更广泛慢性肠病群体与组织病理学确认的慢性炎症性肠病队列的直接比较。总体而言，这些局限性降低了对临床疗效、长期安全性、所提出机制以及粪菌移植适当临床使用相关结论的信心。
11. 结论
粪菌移植是一种生物学上合理且日益标准化的微生物组导向干预措施，适用于伴侣动物。在犬中，最强的临床证据支持在慢性肠病以及特定急性感染性疾病（尤其是犬细小病毒性肠炎）中进行谨慎探索和选择性病例的辅助使用。然而，大多数犬慢性肠病证据仍为观察性、把握度不足或受合并治疗混杂影响，且现有研究包括异质性疾病表型和诊断标准，肠道炎症的组织病理学确认未一致可获得。因此，超越自发缓解、情境效应和标准治疗的确定性疗效尚未确立。在猫中，粪菌移植短期内通常耐受良好，但临床疗效证据仍未得到证实。首项对照猫慢性肠病试验主要终点缺乏显著改善，应缓和临床声明，同时推动采用重复给药、途径比较、表型分层和更长安全性随访的更好设计研究。
机制理解支持涉及微生物定植、代谢恢复、免疫调节以及肠-脑或肠-皮肤轴信号传导的多层次模型，但兽医特异性验证仍然有限。该领域的下一阶段应优先开展把握度充分的假对照试验、标准化产品制备、严格供体筛查、剂量探索研究、长期安全性监测和统一报告标准。有了这些保障措施，粪菌移植可能成为兽医管理微生物组相关疾病的重要辅助手段；当前证据支持谨慎的、产生证据的实施，而非无限制的常规使用或常规一线使用。
致谢
在本稿件的准备过程中，作者使用ChatGPT（GPT-4o，OpenAI）协助进行语言编辑，以提高清晰度和可读性，并协助起草概念性示意图。所有AI辅助材料均由作者进行严格审查、编辑和科学准确性验证，作者对本文的最终内容承担全部责任。
作者贡献
概念构思，J.J.和W.B.；方法学，J.J.和C.X.；文献检索和数据提取，J.J.和C.X.；撰写——初稿准备，J.J.；撰写——审阅和编辑，J.J.和W.B.；监督，W.B.。所有作者均已阅读并同意稿件的发表版本。
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1. Introduction
The gastrointestinal microbiome of companion animals is a metabolically and immunologically active ecosystem that contributes to nutrient processing, mucosal barrier integrity, colonization resistance, bile acid conversion, and immune development [1,2,3,4,5,6]. In dogs and cats, disruption of this ecosystem—commonly described as dysbiosis—is associated with chronic gastrointestinal enteropathies, antibiotic-associated diarrhea, and selected extra-intestinal disorders [2,7]. Dysbiosis is not only a compositional abnormality but also a functional disturbance characterized by altered short-chain fatty acid production, impaired bile acid metabolism, reduced colonization resistance, and expansion of facultative pathogens [2,8,9,10,11]. Chronic gastrointestinal disorders are common reasons for veterinary consultation and referral. In dogs, recent ACVIM-endorsed recommendations favor the term chronic inflammatory enteropathy (CIE) over inflammatory bowel disease (IBD), because canine CIE is not considered directly equivalent to human IBD [12]. However, chronic enteropathy (CE) is a broader clinical term encompassing dogs with persistent or recurrent gastrointestinal signs, including populations in which intestinal biopsy and histopathological confirmation of inflammation may not be available. Because the canine FMT literature reviewed here includes both histopathologically confirmed inflammatory enteropathy and broader chronic enteropathy populations, we use CE as the overarching term throughout the clinical evidence synthesis. CIE is reserved for histopathologically supported inflammatory enteropathy, for terminology specifically defined by current consensus guidance, or for study populations explicitly characterized as CIE. IBD is retained only where it reflects terminology used in the original publication or established disease activity indices.
Canine chronic enteropathy comprises heterogeneous and multifactorial disease phenotypes involving interactions among diet, the intestinal microbiota, mucosal immunity, environmental factors, and host susceptibility. Canine chronic enteropathies have traditionally been categorized according to treatment response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), immunosuppressant-responsive enteropathy (IRE), and non-responsive enteropathy (NRE). However, recent advances have challenged this framework. In particular, a refined classification has proposed replacing ARE with microbiota-related modulation-responsive enteropathy (MrMRE), reflecting decreasing reliance on empirical antimicrobial therapy and increasing use of microbiota-directed approaches, including prebiotics, probiotics, postbiotics, dietary modulation, and fecal microbiota transplantation (FMT) [13]. More recent ACVIM-endorsed guidance continues to emphasize phenotyping according to treatment response, including food-responsive CIE (CIE-FR) and immunosuppressant-responsive CIE (CIE-IR) [12]. Although clinical signs may improve following dietary, microbiota-directed, or immunomodulatory interventions, underlying microbial and metabolic abnormalities may persist [2,8,14,15,16,17,18,19]. In cats, chronic enteropathy (CE) remains the broader clinical term, and the diagnostic overlap between inflammatory chronic enteropathies and small-cell intestinal lymphoma creates additional complexity [20,21]. FMT involves the transfer of processed fecal material from a healthy, screened donor to a recipient with disease. In human medicine, FMT is best established for recurrent Clostridioides difficile infection [22,23,24,25,26,27,28], with additional but more variable evidence in inflammatory bowel disease, including ulcerative colitis, and in metabolic disorders [29,30,31,32,33,34,35,36,37,38]. The application of FMT in veterinary medicine, however, requires caution because dogs and cats differ from humans in diet, gastrointestinal anatomy, bile acid profiles, core microbial taxa, pathogen risks, and regulatory context. Veterinary FMT should therefore be evaluated on the basis of species-specific clinical evidence rather than by direct extrapolation from human studies [2,39].
Interest in FMT for companion animals has increased because the intervention targets the intestinal microbial community as an ecological system rather than a single pathogen or isolated probiotic strain. Potential therapeutic effects include donor microbial engraftment, suppression of pathobionts, restoration of microbial metabolites, improved epithelial barrier function, immune modulation, and systemic signaling through gut–skin and gut–brain axes [39,40,41,42,43,44,45,46,47,48,49]. However, most veterinary studies remain small, uncontrolled, or heterogeneous in design, and interpretation is further limited by concurrent treatments, lack of blinding, reliance on subjective or owner-reported outcomes in some studies, incomplete follow-up, and substantial variation in donor selection, FMT preparation, route of administration, dose, and treatment frequency. These factors make it difficult to attribute clinical improvement specifically to FMT. FMT may influence recipient health through microbial community restructuring, colonization resistance, metabolic restoration, barrier and immune modulation, and extra-intestinal gut–skin or gut–brain signaling. The strength of evidence for these pathways varies by species, indication, formulation, delivery route, and study design, and they should therefore not be regarded as equally established mechanisms. These proposed mechanisms and their varying levels of evidential support are summarized in Figure 1.
[图：Proposed mechanisms and evidence framework for FMT in dogs and cats.]
Previous reviews of FMT in companion animals have generally been limited by species, clinical indication, or emphasis on microbiome mechanisms, and few have integrated recent clinical evidence with developments in treatment delivery, preparation, safety, and standardization. Importantly, the veterinary FMT literature has also evolved substantially over time. Earlier evidence was dominated by individual case reports, small case series, and predominantly rectal administration, whereas more recent studies increasingly include prospective cohorts, randomized or controlled trials, repeated-treatment protocols, and orally administered lyophilized preparations. Outcome assessment has likewise expanded from predominantly clinical observations to include validated disease activity indices, dysbiosis measures, microbiome profiling, and donor–recipient microbial engraftment. Recent studies have also broadened the range of investigated indications, while providing more systematic information on tolerability, donor screening, and treatment standardization. The present review therefore not only synthesizes the current evidence for FMT in dogs and cats but also examines how the field has evolved with respect to clinical indications, routes and formulations of administration, treatment protocols, clinical and microbiome-related responses, adverse effects, and methodological rigor. By explicitly distinguishing controlled from uncontrolled evidence and identifying changes in both clinical application and study design, we aim to clarify which developments may already be relevant to clinical decision-making and which should primarily inform future research. The principal contribution of this review is thus a cross-species and temporally contextualized framework linking clinical outcomes, mechanistic plausibility, product standardization, and safety considerations.
2. Materials and Methods
2.1. Review Design and Scope
This article was designed as a structured narrative review of FMT in companion animals, with primary emphasis on dogs and cats. The review aimed to synthesize clinically relevant evidence while also integrating selected mechanistic, methodological, and safety literature needed to interpret the veterinary FMT field. Because the available studies varied substantially in design, indication, delivery route, dosing protocol, and outcome measures, a meta-analysis was not appropriate. The review was not registered as a systematic review protocol and did not include a formal risk-of-bias assessment.
Eligible publications included peer-reviewed original studies, controlled trials, cohort studies, case series, case reports, microbiome or metabolomic studies, safety reports, clinical guidelines, preparation protocols, and relevant reviews involving FMT in dogs, cats, or companion-animal contexts. Studies focused exclusively on livestock, laboratory animals, or wildlife were excluded unless they provided methodological or safety information directly relevant to companion-animal FMT. Conference abstracts without full peer-reviewed manuscripts and studies limited to probiotics, prebiotics, antibiotics, or diet without FMT were excluded from the core FMT evidence synthesis, although selected non-FMT microbiome interventions were discussed for comparative context.
2.2. Literature Search and Evidence Synthesis
Literature was identified through structured searches of PubMed/MEDLINE, PubMed Central, and Web of Science for publications from January 2005 to May 2026, with the final search conducted in May 2026. Search terms combined FMT-related terminology with species and disease terms, including “fecal microbiota transplantation”, “faecal microbiota transplantation”, “fecal microbial transplantation”, “faecal microbial transplantation”, “FMT”, “fecal transplant”, “stool transplant”, “dog”, “canine”, “cat”, “feline”, “companion animal”, “chronic enteropathy”, “chronic inflammatory enteropathy”, “protein-losing enteropathy”, “dysbiosis”, “diarrhea”, and “donor screening”. Database-specific syntax was adjusted according to the indexing and search functions of each platform, while the same core concepts and eligibility framework were retained across databases. Database-specific search strategies were developed for each platform based on the following core concepts: (“fecal microbiota transplantation” OR “faecal microbiota transplantation” OR FMT OR “fecal transplant” OR “stool transplant”) AND (dog OR canine OR cat OR feline OR “companion animal”) AND (enteropathy OR diarrhea OR dysbiosis OR “donor screening” OR safety). Reference lists of key reviews, clinical studies, and companion-animal FMT guidelines were screened manually to identify additional relevant publications. The core clinical evidence synthesis included 22 selected companion-animal FMT clinical reports or studies, including 17 canine and 5 feline studies. Additional clinical reports were discussed where relevant to specific applications, administration routes, or methodological considerations.
Screening, study selection, and data extraction were performed by the authors. The included studies were peer-reviewed original clinical reports describing FMT administration in dogs or cats within the predefined publication period. Conference abstracts without a full peer-reviewed manuscript, studies not involving FMT, and non-clinical reviews or methodological papers were excluded from the core clinical study count. Eligibility was not determined by study outcome, sample size, administration route, or completeness of reporting. For included studies, species, indication, study design, FMT preparation and route, clinical and microbiome outcomes, adverse events, follow-up, and major limitations were extracted where reported. Evidence was classified descriptively, based on study design, presence or absence of a control group, sample size, follow-up duration, objective microbiome or metabolomic endpoints, and susceptibility to confounding by concurrent therapy. The following narrative evidence categories were used throughout the review: controlled veterinary clinical evidence, uncontrolled veterinary clinical evidence, mechanistic veterinary evidence, and extrapolated or hypothesis-generating evidence. No formal risk-of-bias tool or GRADE assessment was applied; therefore, evidence labels in the text and tables should be interpreted as descriptive evidence categories rather than formal certainty ratings.
3. The Companion-Animal Gut Microbiome: Health, Dysbiosis, and Diagnostic Assessment
3.1. Healthy Canine and Feline Microbiomes
Culture-independent sequencing of fecal samples has shown that healthy dogs exhibit a range of fecal microbial profiles commonly characterized by Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria [50,51]. Fusobacterium is a notable example of species-specific interpretation: in dogs, it is often abundant in healthy fecal communities and may contribute to protein and amino acid fermentation, whereas in humans, some Fusobacterium species are more often discussed in disease contexts [2,50]. Large-scale canine sequencing studies have refined species-level definitions of core taxa and highlighted the influence of diet, age, and breed on microbial structure [52,53,54]. Importantly, fecal microbial profiles should not be assumed to fully represent mucosa-associated or more proximal intestinal communities.
Cats share some dominant bacterial phyla with dogs but differ in microbial proportions and metabolic context, consistent with their obligate carnivory [1,55,56]. These differences are clinically important because donor screening, donor–recipient matching, and outcome interpretation should be species-specific. A donor profile considered healthy for a cat should not be assumed to restore a healthy canine microbiome, and vice versa.
3.2. Dysbiosis and Functional Consequences
Dogs with chronic inflammatory enteropathy (CIE) commonly show expansion of Proteobacteria, including Escherichia coli, depletion of Fusobacteria, and reductions in Firmicutes taxa within Clostridia clusters XIVa and IV [57,58,59]. However, increased relative abundance of E. coli should not be interpreted as evidence of pathogenicity, because commonly used 16S rRNA sequencing and broad qPCR approaches generally cannot reliably distinguish commensal from pathogenic strains. These compositional changes are accompanied by functional disturbances, including reduced fecal concentrations of acetate, propionate, and total short-chain fatty acids, as well as altered bile acid conversion due in part to depletion of Clostridium hiranonis [8,9]. However, fecal short-chain fatty acid concentrations do not directly reflect intestinal production because they are also influenced by host absorption, microbial utilization, intestinal transit, diet, and stool water content. Alterations in short-chain fatty acid availability may therefore contribute to impaired epithelial and immune homeostasis, although fecal concentrations alone cannot establish reduced intestinal production [8,60,61,62,63,64].
Feline dysbiosis is less extensively characterized, but cats with chronic enteropathy, particularly inflammatory phenotypes, or small-cell intestinal lymphoma show microbial patterns that may have diagnostic and prognostic relevance [20,21,65,66,67]. Antibiotic-associated dysbiosis is also clinically relevant in companion animals. Metronidazole can disrupt microbiome composition and metabolic profiles beyond the treatment period, creating a rationale for interventions that restore microbial function rather than merely resolving diarrhea [68,69].
3.3. Dysbiosis Index as a Clinical and Research Tool
The qPCR-based Dysbiosis Index (DI) provides a practical summary measure of changes in a predefined bacterial panel associated with fecal dysbiosis. It does not capture the entire intestinal microbiome or all forms of dysbiosis and should therefore be interpreted as a complementary rather than comprehensive microbiome measure. In dogs, the DI uses selected bacterial targets and total bacterial abundance and has shown diagnostic utility in distinguishing dogs with CIE from healthy dogs [70]. The DI has become a common endpoint in canine FMT studies and may help identify patients more likely to respond; several studies suggest that baseline dysbiosis severity is associated with treatment outcome [71,72]. A feline DI has also been developed and is increasingly used in feline microbiome studies [73].
These tools are valuable because they provide objective endpoints beyond owner-reported clinical signs. However, DI results should be interpreted alongside clinical activity scores, diet, medication history, antimicrobial exposure, and disease phenotype. Canine and feline fecal microbiomes share several dominant bacterial phyla but differ in microbial proportions and metabolic context, supporting species-specific interpretation of donor profiles and FMT outcomes. Dysbiosis may involve shifts in bacterial composition together with altered short-chain fatty acid concentrations, bile acid conversion, epithelial barrier function, and immune regulation. These relationships are summarized in Figure 2.
[图：Species-specific healthy gut microbiomes, dysbiosis-associated functional disruption, and diagnostic assessment in dogs ]
4. FMT in Canine Medicine
Canine FMT evidence has expanded from isolated case reports to prospective cohorts, multicenter studies, and small randomized trials. Table 1 summarizes selected clinical studies and indicates study design as a practical evidence-level marker. Overall, the clinical literature is most developed for canine chronic enteropathy (CE), although the enrolled populations vary in diagnostic characterization, and histopathological confirmation of intestinal inflammation was not required or available in all studies. Most available evidence remains observational, uncontrolled, or underpowered, and controlled findings are still limited and heterogeneous. The strongest controlled evidence comes from selected acute infectious settings, particularly canine parvoviral enteritis, whereas evidence for other acute diarrheal syndromes remains mixed.
Table 1. Summary of selected canine FMT clinical studies, with study design reported descriptively.
| Study | Design | n | Indication | Route | Key Outcome |
|---|---|---|---|---|---|
| Pereira et al. [ 74 ] | RCT | 66 | Canine parvovirus enteritis | Enema | Faster diarrhea resolution; shorter hospitalization |
| Niina et al. [ 75 ] | Case report | 1 | Refractory CE (histopathologically confirmed CIE; reported as IBD in the original study) | Repeated enema | CIBDAI improved from 9 to 4; Proteobacteria decreased |
| Chaitman et al. [ 76 ] | Prospective treatment trial | 18 | Acute diarrhea | Enema | DI decreased after FMT, whereas dysbiosis persisted after metronidazole at day 28 |
| Niina et al. [ 77 ] | Uncontrolled clinical study | 9 (16S sequencing in 3) | CE (histopathologically confirmed CIE; reported as IBD in the original study) | Single rectal enema | CIBDAI decreased and Fusobacterium increased after FMT |
| Gal et al. [ 78 ] | Pilot study | 8 | AHDS | Enema | No additional benefit over standard care |
| Collier et al. [ 79 ] | Double-blind randomized clinical trial | 13 (7 FMT; 6 placebo) | CE (histopathologically confirmed CIE; reported as IBD in the original study) | Single retention enema | CCECAI decreased over time in both groups; no significant between-group difference |
| Cerquetella et al. [ 80 ] | Case report | 1 | Relapsing diarrhea | Oral capsules | Clinical improvement with no serious relapses during 18-month follow-up; maintenance prednisolone was continued |
| Toresson et al. [ 71 ] | Retrospective case series | 41 | CE | Enema | 31/41 dogs improved; lower baseline DI was associated with better response |
| Sugita et al. [ 81 ] | Uncontrolled trial | 12 | Atopic dermatitis | Single oral administration | CADESI-04 improved; exploratory extra-intestinal signal |
| Brugnoli et al. [ 82 ] | Prospective multicenter cohort | 171 enrolled; 111 analyzed | CE | Oral lyophilized capsules | 82% response among analyzed dogs; missing outcome data and absence of a control group limit inference |
| Hanifeh et al. [ 83 ] | Double-blind RCT | 13/14 analyzed | Tylosin-responsive enteropathy | Oral capsules | 71.4% non-relapse after FMT vs. 50% after placebo; difference not statistically significant |
| Rojas et al. [ 84 ] | Cohort | 54 | Chronic gastrointestinal signs | Oral capsules | 18% donor–recipient ASV sharing; Butyricicoccus increased |
| Pérez-Accino et al. [ 85 ] | Prospective uncontrolled study | 7 | CE (histopathologically confirmed CIE) | Rectal FMT | Clinical severity decreased after FMT; improvement was not accompanied by consistent longitudinal changes in fecal microbial community composition or diversity |
| Vecchiato et al. [ 86 ] | Prospective multicenter | 20 | Diet-refractory CE | Enema | Median CIBDAI improved from 5 to 1; 17/20 improved at 3 months |
| Toresson et al. [ 72 ] | Prospective longitudinal | 39 | Refractory CE | Repeated enemas | 28/39 responded; corticosteroid dose reduced in 13 dogs |
| Schreiber et al. [ 87 ] | Case report | 1 | Protein-losing enteropathy with concurrent protein-losing nephropathy | Repeated enema and oral lyophilized FMT | Repeated FMT was associated with improvement in clinical status, body weight, serum albumin, fecal consistency, and DI; repeated treatment was required to maintain the response |
| Allerton et al. [ 88 ] | Blinded randomized controlled trial | 42 (25 FMT; 17 control) | CE | Single retention enema | No significant additional clinical benefit of FMT plus dietary management over dietary management alone for owner-reported improvement, CIBDAI, or fecal score |
4.1. Chronic Enteropathy and Related Phenotypes
The most extensively studied canine indication for FMT is chronic enteropathy (CE), although the diagnostic work-up and availability of histopathological confirmation vary among studies. Retrospective and prospective studies have reported reductions in CIBDAI or related disease activity scores after FMT, particularly in protocols involving repeated administrations [71,72,86]. Toresson et al. reported clinical improvement in 31 of 41 dogs with CE receiving adjunctive enema-based FMT and identified lower baseline Dysbiosis Index (DI) as a potential predictor of response [71]. Vecchiato et al. subsequently reported clinical improvement in 17 of 20 dogs with diet-refractory CE in a prospective multicenter study, with median CIBDAI decreasing from 5 to 1 [86]. In a prospective longitudinal study of dogs with refractory CE, repeated FMT was associated with clinical response in 28 of 39 dogs and reduced corticosteroid use in a subset of cases [72]. Microbiome-related endpoints, including changes in the DI, bacterial abundance, or donor–recipient ASV sharing, should be interpreted separately from clinical outcomes and do not by themselves demonstrate clinical efficacy.
Oral lyophilized capsules may improve practicality by enabling repeated outpatient dosing. Brugnoli et al. reported an 82% positive clinical response among 111 analyzable dogs with CE treated with oral lyophilized FMT capsules from an initial prospective multicenter cohort of 171 dogs [82]. This result is clinically encouraging, but the uncontrolled design, substantial missing post-treatment data, and lack of a placebo control mean that causal interpretation should remain cautious.
Randomized evidence remains limited. Collier et al. randomized 13 dogs with histopathologically confirmed CIE, reported as IBD in the original publication, to FMT or placebo in addition to standard therapy. CCECAI decreased over time in both groups, with a numerically greater reduction in the FMT group, but no significant between-group difference was detected [79]. Hanifeh et al. provided double-blind proof-of-concept evidence in dogs with tylosin-responsive enteropathy (using the treatment-response terminology of the original study), reporting fewer relapses after oral FMT capsules than after placebo, although the sample size was small [83].
Taken together, current canine data support further investigation of FMT as a microbiome-directed adjunct, but do not yet establish definitive clinical efficacy. Most positive findings derive from observational or small studies, and causal interpretation remains limited by heterogeneous protocols, concurrent treatments, and limited controlled replication. Larger sham-controlled trials with standardized donor screening, dose-finding, controlled background therapy, objective microbiome endpoints, and relapse-free survival outcomes are needed before FMT can be recommended as routine treatment for canine CE.
4.2. Acute Diarrhea, Parvovirus, and Acute Hemorrhagic Diarrhea Syndrome
The strongest controlled canine evidence in acute gastrointestinal disease comes from canine parvoviral enteritis. In a randomized controlled trial of 66 puppies, enema-based FMT accelerated diarrhea resolution and shortened hospitalization compared with standard care alone [74]. This finding is clinically important because it used meaningful clinical endpoints in a high-morbidity infectious disease context.
In non-specific acute diarrhea, a prospective non-randomized treatment trial comparing FMT with metronidazole found that clinical signs improved in both groups, while microbiome recovery was more evident after FMT [76]. This distinction highlights the difference between symptomatic resolution and microbiome recovery. Conversely, a pilot study in acute hemorrhagic diarrhea syndrome found no additional benefit from a single enema-based FMT over standard supportive care [78]. These mixed findings suggest that timing, disease mechanism, dose, frequency, and route of administration may strongly influence outcomes in acute gastrointestinal disease.
4.3. Extra-Intestinal Applications
Early studies have explored FMT beyond gastrointestinal disease. Sugita et al. reported improved CADESI-04 scores after a single oral FMT in dogs with atopic dermatitis [81], and Watanangura et al. reported changes in behavioral comorbidities and urinary neurotransmitter profiles in dogs with drug-resistant epilepsy [89]. These findings are hypothesis-generating rather than practice-changing, but they are consistent with broader concepts of gut–skin and gut–brain axis signaling [2,45].
Extra-intestinal applications should currently be considered exploratory. Future studies should include randomized controls, validated dermatological or neurological endpoints, control of concurrent medications, metabolomic assessment, and longitudinal microbiome profiling to determine whether clinical changes are reproducible and mechanistically linked to FMT.
4.4. Oral Lyophilized FMT as a Practical Advance
Fresh or frozen enema-based FMT can deliver a high microbial dose directly to the distal gut, but it often requires restraint, sedation, immediate product handling, or referral-center infrastructure. Oral lyophilized capsules address several practical limitations by allowing repeated outpatient or owner-administered dosing under veterinary supervision, easier storage, and batch-level quality control. Pilot work supports feasibility and tolerability in dogs [90], and capsule-based studies have demonstrated measurable donor microbial signals [83,84]. Key unresolved questions include optimal dose, treatment duration, capsule viability, donor selection, engraftment consistency, and whether passage through the upper gastrointestinal tract alters efficacy compared with rectal administration.
5. FMT in Feline Medicine
Feline FMT research remains very limited, with few clinical studies and limited controlled evidence. Available studies are constrained by small sample sizes, heterogeneous indications, uncontrolled designs, subjective or owner-reported outcomes in some studies, and incomplete follow-up. Although microbiome changes have been reported after FMT, these findings should not be interpreted as evidence of therapeutic benefit, and clinical efficacy has not yet been established. Table 2 summarizes selected feline reports and trials and distinguishes controlled from uncontrolled evidence.
Table 2. Summary of selected feline FMT studies, with study design reported descriptively.
| Study | Design | n | Indication | Route | Key Outcome |
|---|---|---|---|---|---|
| Furmanski and Mor [ 91 ] | Case report | 1 | Refractory ulcerative colitis | Enema | Sustained remission reported for 11 months |
| Rojas et al. [ 92 ] | Observational microbiome cohort | 46 | Chronic digestive signs | Oral capsules | ~13% donor–recipient ASV sharing; microbiome shifted toward healthy reference profiles in some cats |
| Karra et al. [ 93 ] | Prospective blinded controlled trial | 28 | Chronic enteropathy | Single enema | Well tolerated; no significant DI or FCEAI improvement versus controls |
| Lee et al. [ 94 ] | Retrospective case series | 9 | CE or therapy-resistant diarrhea | Repeated rectal enemas | Predominantly grade I–II AEs; one grade III severe abdominal pain event; 8/9 cats showed complete or partial clinical response |
| Martini et al. [ 95 ] | Randomized experimental study | 25 | Metronidazole-induced dysbiosis in healthy adult cats | Oral FMT capsules plus diet | FMT was the only intervention to normalize DI, although the effect was transient in some cats |
5.1. Chronic Enteropathy and Chronic Digestive Signs
The first documented feline case report described sustained remission in a cat with refractory ulcerative colitis after two enema-based FMT procedures [91]. Larger experience has come from oral capsule studies in cats with chronic vomiting, diarrhea, or constipation. Rojas et al. reported microbiome-level changes in 46 cats with chronic digestive signs, including donor–recipient shared ASVs and shifts toward healthier reference profiles in some animals [92]. Because the study was uncontrolled and primarily focused on microbiome outcomes, these findings should not be interpreted as evidence of clinical efficacy.
The first prospective, blinded, controlled feline chronic enteropathy trial did not demonstrate significant improvement in Dysbiosis Index (DI) or Feline Chronic Enteropathy Activity Index (FCEAI) after a single enema-based FMT compared with control treatment [93]. This negative controlled result is important because it prevents overinterpretation of uncontrolled feline case reports and observational cohorts. The FCEAI provides a relevant clinical activity measure [96], whereas the diagnostic overlap among feline inflammatory and low-grade neoplastic enteropathies remains an important interpretive challenge [97]. Possible explanations for the neutral FMT result include insufficient sample size, single-dose exposure, enema-only delivery, concurrent standard therapy in both groups, and heterogeneity among feline CE phenotypes. Future feline trials should therefore evaluate repeated dosing, oral versus rectal delivery, phenotype stratification, and longer follow-up before efficacy claims are made.
Accordingly, current feline evidence should be interpreted as supporting biological activity and short-term tolerability rather than established clinical efficacy. Microbiome changes alone should not be considered evidence of therapeutic benefit, and the available evidence is insufficient to establish long-term safety. Routine clinical use in cats should remain cautious and preferably evidence-generating until repeated-dose, sham-controlled, phenotype-stratified trials with longer follow-up are available.
5.2. Experimental Recovery from Antibiotic-Associated Dysbiosis
A randomized experimental study in 25 healthy adult cats treated with metronidazole found that FMT was the only intervention to normalize the feline Dysbiosis Index (DI) immediately after the intervention, although this effect appeared transient in some cats [95]. Because this study used experimentally induced antibiotic-associated dysbiosis in healthy cats rather than naturally occurring chronic enteropathy, its findings support a microbiome-level biological effect of FMT but should not be interpreted as evidence of clinical efficacy in cats with chronic enteropathy. Future clinical studies should evaluate repeated dosing, oral versus rectal delivery, disease phenotype stratification, and long-term follow-up after antimicrobial discontinuation.
5.3. Safety and Donor Screening in Cats
Available feline safety data are limited. Lee et al. reported predominantly grade I–II adverse events after enema-based FMT in nine cats, with one grade III event involving severe abdominal pain; most adverse events resolved with supportive care or no intervention [94]. The controlled feline CE trial also reported tolerability without serious adverse events [93]. Feline donor screening should be stricter than canine screening in several respects, including testing for feline immunodeficiency virus, feline leukemia virus, and Tritrichomonas foetus, in addition to bacterial pathogens, parasites, and antimicrobial-resistant organisms [98].
6. Preparation, Standardization, and Clinical Guidelines
6.1. Donor Screening and Safety Safeguards
Donor screening is a key component of FMT safety, but safe clinical use also depends on appropriate recipient selection, standardized processing, batch quality control and traceability, appropriate administration, and systematic adverse-event monitoring. Companion-animal FMT guidelines recommend screening for enteric bacterial pathogens such as Salmonella, Campylobacter, Clostridioides difficile, Clostridium perfringens, and extended-spectrum beta-lactamase-producing Escherichia coli; parasites such as Giardia and Cryptosporidium; and species-specific viral or protozoal pathogens where relevant [98,99,100]. Culture-based screening, targeted molecular assays, and broader resistome analysis provide complementary but non-equivalent information; therefore, a negative selective culture does not exclude all resistant organisms or antimicrobial-resistance genes. Donor programs should define a minimum screening panel, periodic re-screening intervals, exclusion criteria, and procedures for positive results, including temporary or permanent donor exclusion and re-evaluation before further use. Donors should also be clinically healthy, free of recent antimicrobial exposure, and maintained on a stable diet.
At a minimum, future clinical protocols should report donor health criteria, recent antimicrobial exposure, diet stability, screening panels, re-screening intervals, fecal handling time, storage conditions, batch identifiers, recipient monitoring, and adverse-event grading. For cats, donor programs should explicitly include feline-specific infectious disease screening in addition to the enteric pathogen and antimicrobial-resistance safeguards used across companion animals.
Because FMT transfers a complex and incompletely characterized biological product, negative pathogen tests cannot eliminate all risk. Safety programs should therefore include donor re-screening intervals, batch traceability, recipient monitoring, adverse-event reporting, and, where feasible, antimicrobial-resistance gene surveillance.
6.2. Fresh, Frozen, and Lyophilized Preparations
Microbial DNA abundance does not necessarily reflect viable microbial load, and preservation of overall viability may still be accompanied by selective loss of sensitive taxa. Therefore, microbial viability and product standardization depend not only on whether a preparation is fresh, frozen, or lyophilized, but also on processing conditions, storage, oxygen exposure, and product-specific validation. Fresh preparations may maximize viability but require rapid processing and administration. Frozen preparations improve scheduling flexibility but require validated cryoprotectants and cold-chain storage. Lyophilized preparations offer the greatest practical standardization and support oral capsule delivery, although viability, dose equivalence, engraftment consistency, and long-term stability require continued validation [101]. The practical differences among fresh, frozen, and lyophilized FMT preparations are summarized in Table 3.
Table 3. Practical comparison of FMT preparation methods for companion animals and their likely clinical-use scenarios.
| Parameter | Fresh | Frozen | Lyophilized |
|---|---|---|---|
| Viability | Generally highest immediately after processing | High if cryoprotectant and storage are optimized | Good when validated; product-specific |
| Storage | Hours; immediate use preferred | Usually ultra-low temperature storage | Room temperature or refrigerated storage may be possible depending on product |
| Convenience | Low; same-day preparation | Moderate; cold chain required | High; capsules and batch production possible |
| Standardization | Difficult | Moderate | Highest potential |
| Main limitation | Logistics and donor availability | Storage and thawing effects | Dose equivalence, viability, and regulatory classification |
6.3. Rectal/Enema Administration of FMT
Rectal or enema administration is one of the commonly used routes of FMT in veterinary medicine and has been applied in both dogs and cats. In addition to the studies discussed above, Ural et al. reported extensive clinical experience with predominantly rectal FMT in dogs with various disease conditions [102], while rectal FMT has also been investigated in cats with ataxia [103]. These studies provide additional clinical experience regarding the feasibility of rectal FMT, although further controlled studies are required to establish its efficacy across different indications.
6.4. Regulatory and Commercial Standardization
The field is moving from case-by-case clinical preparation toward standardized protocols and commercial capsule products. This transition may improve reproducibility, quality control, accessibility, and treatment adherence, but it also raises important regulatory questions. Veterinary FMT products do not yet have a clearly harmonized regulatory pathway, and their classification as biological products, veterinary medicinal products, supplements, or compounded preparations remains context dependent. Clear product classification, minimum donor screening requirements, batch-release criteria, labeling standards, adverse-event reporting systems, and antimicrobial-resistance surveillance are needed before broader clinical adoption [98,101,104].
7. Mechanisms of Action
FMT is unlikely to act through a single mechanism. A multi-level model is more plausible: donor microorganisms may partially engraft, recipient microbial communities may be restructured, microbial metabolic functions may recover, barrier and immune functions may improve, and systemic signaling may influence extra-intestinal outcomes. However, the evidentiary basis differs across these mechanisms. In companion animals, direct support is strongest for measurable microbiome shifts and is emerging for metabolic endpoints, whereas immune modulation and gut–skin or gut–brain signaling remain supported mainly by human, experimental, or hypothesis-generating veterinary data. In companion animals, direct evidence is strongest for measurable microbiome shifts and donor–recipient microbial sharing, emerging for metabolic restoration, and limited or hypothesis-generating for immune-mediated and extra-intestinal effects. These interconnected mechanisms and their differing levels of evidence are summarized in Figure 3. Post-treatment microbiome changes should not be assumed to be donor-derived or mechanistically responsible for clinical improvement, particularly in uncontrolled studies in which diet, antimicrobial withdrawal, concurrent treatment, spontaneous recovery, and temporal variation may also contribute.
[图：Proposed multi-level mechanisms of FMT in companion animals.]
7.1. Microbial Engraftment and Community Restructuring
Strain-level, longitudinal evidence provides the strongest support for donor engraftment, whereas shared ASVs alone should not be considered confirmation of engraftment. Human metagenomic studies show that donor strain engraftment varies by disease, donor–recipient compatibility, and microbial taxa, and that higher engraftment can be associated with better outcomes [40]. Veterinary data are emerging: oral FMT studies have reported measurable donor ASV sharing in dogs and cats, although rates were modest [84,92]. Shared ASVs may represent multiple strains, pre-existing taxa below the detection threshold, or taxa common in the wider population. Partial engraftment should not be dismissed, because ecological effects may also arise through transient colonization, cross-feeding, phage transfer, metabolite shifts, and suppression of pathobionts [41]. Accordingly, post-treatment community shifts, demonstrable donor-derived engraftment, and microbiome changes that mediate clinical improvement should be regarded as distinct levels of evidence.
7.2. Metabolic Restoration
Metabolic restoration may be as important as compositional change. Dogs with CIE show reduced fecal short-chain fatty acids and altered bile acid metabolism [8,9]. Recovery of short-chain fatty acid-producing organisms may support colonocyte energy supply, epithelial tight-junction integrity, and regulatory immune pathways. Recovery of Clostridium hiranonis or other bile acid-converting organisms may influence primary-to-secondary bile acid conversion and inflammation-related receptor signaling [2,9,48,105,106,107]. However, species-specific bile acid pools and diet-associated fermentation patterns mean that canine, feline, and human mechanisms cannot be assumed to be identical.
7.3. Immune Modulation and Barrier Function
FMT may reduce mucosal immune activation by increasing colonization resistance, decreasing pathogen-associated antigenic stimulation, improving epithelial barrier function, and promoting regulatory immune pathways [22,42,43,44,61,108,109,110,111,112]. In dogs and cats, however, direct evidence that these immunological changes mediate clinical response remains limited. Future veterinary studies should include mucosal cytokine profiling, regulatory T-cell markers, secretory immunoglobulin A, histopathology, metabolomics, and longitudinal clinical endpoints to test whether immunological changes precede or simply accompany clinical improvement.
7.4. Gut–Skin and Gut–Brain Axis Signaling
Exploratory canine studies in atopic dermatitis and epilepsy are consistent with gut–skin and gut–brain axis hypotheses [81,89]. Candidate mediators include microbial metabolites, neuroactive compounds, vagal signaling, hypothalamic–pituitary–adrenal axis effects, and systemic immune modulation [2,45,49]. These applications should be treated as mechanistic leads rather than established indications until controlled trials replicate clinical benefits and define biomarkers of response.
8. FMT Compared with Other Microbiome-Modulating Therapies
8.1. Probiotics and Prebiotics
Probiotics and prebiotics are easier to regulate, administer, and standardize than FMT, but their effects are typically strain-specific, substrate-specific, condition-specific, and often transient [18,113,114,115,116,117]. Some probiotic trials in dogs and cats have reported benefits for acute diarrhea, fecal consistency, or selected gastrointestinal outcomes, but systematic reviews generally rate the evidence as limited, heterogeneous, or of variable clinical relevance [113,114,118,119]. Prebiotics may support endogenous microbial activity through selective substrate provision, but they do not directly replace a disrupted microbial community. FMT differs conceptually because it transfers a complex microbial ecosystem, including multiple viable taxa and associated functional capacity, rather than one or a few selected organisms or substrates. However, direct comparisons should be made cautiously because the probiotic evidence base includes systematic reviews and controlled trials, whereas much of the veterinary FMT evidence remains based on small or uncontrolled studies. Both approaches should therefore be evaluated using comparable criteria, including study quality, effect size, safety, durability, and clinical relevance.
8.2. Postbiotics, Phage Therapy, and Defined Consortia
Postbiotics, bacteriophage therapy, and defined microbial consortia may eventually offer more precise and standardized alternatives to whole-stool FMT [48,110,120,121,122,123,124]. Postbiotics avoid the risks associated with transfer of live organisms, phages can be designed or selected to target specific bacterial pathogens, and defined consortia can be manufactured with known composition and quality-control specifications. Whether the ecological complexity of whole-community FMT provides a clinically meaningful advantage over more targeted microbiome-based approaches remains uncertain. Comparative studies are needed to determine which patients require broad ecosystem-level intervention and which may respond adequately to targeted microbiome-derived products.
8.3. Practical Clinical Positioning
At present, documented dysbiosis, refractory or relapsing gastrointestinal disease, antibiotic-associated dysbiosis, and incomplete response to appropriate diet or conventional therapy should be regarded as potential clinical contexts for investigation rather than validated indications for FMT. Similarly, the severity or normalization of the Dysbiosis Index should not be assumed to predict or confirm clinical response. FMT should not replace diagnostic work-up, dietary trials, parasite control, antimicrobial stewardship, or immunosuppressive treatment when these are indicated. When used outside controlled trials, clinicians should apply standardized donor screening, batch traceability, adverse-event monitoring, and owner-informed consent, and should frame the intervention as evidence-generating rather than definitively established for most indications. In clinical research, microbiome endpoints such as the Dysbiosis Index should be interpreted together with disease activity scores, medication reduction, relapse-free survival, adverse-event monitoring, and quality-of-life measures.
9. Knowledge Gaps and Future Directions
9.1. Main Evidence Gaps
The central evidence gap is the lack of adequately powered, randomized, sham-controlled trials evaluating FMT in canine and feline CE. Existing studies are often small, uncontrolled, retrospective, or confounded by concurrent standard therapy [71,72,79,82,88,93]. In canine studies, additional heterogeneity arises from differences in diagnostic work-up and the inconsistent availability of histopathological confirmation of intestinal inflammation. This limitation is particularly important in feline medicine, where the number of controlled studies and enrolled animals remains small. Dosing and delivery protocols are also largely empirical. Published studies differ in the use of fresh, frozen, or lyophilized material; enema versus oral administration; single versus repeated dosing; donor selection; background diet; concurrent medications; and duration of follow-up.
Long-term safety remains insufficiently characterized. Most veterinary studies report outcomes over days to months, and only isolated reports provide longer follow-up [80]. Key unresolved issues include the durability of donor microbial engraftment, timing and predictors of relapse, effects on antimicrobial-resistance gene carriage, risk of zoonotic pathogen transfer, and safety in immunocompromised patients or animals with severe intestinal inflammation. The welfare and ethical management of donor animals also warrant consideration, particularly where donor eligibility may involve restrictive housing, dietary control, or repeated fecal collection.
9.2. Research Priorities
Priority 1: Adequately powered, sham-controlled randomized trials in canine and feline CE, with standardized background therapy, clearly defined diagnostic criteria, phenotypic stratification, explicit reporting of histopathological confirmation where available, and prespecified clinically meaningful endpoints.
Priority 2: Head-to-head route and dosing studies comparing enema, oral capsule, and combined protocols while controlling microbial dose, viability, dosing frequency, and treatment duration.
Priority 3: Multi-omics mechanistic studies integrating metagenomics, metabolomics, bile acid profiling, short-chain fatty acid measurement, immunophenotyping, and validated clinical activity scores.
Priority 4: Donor optimization studies comparing universal donors, pooled donors, diet-matched donors, microbiome-defined donors, and pathogen- and antimicrobial-resistance-screened donor programs, while also considering donor welfare and ethical management.
Priority 5: Long-term safety surveillance extending to at least 12 months, including relapse, adverse events, antimicrobial-resistance markers, microbiome durability, and owner-reported quality-of-life outcomes.
9.3. Reporting Standards and One Health Considerations
Veterinary FMT studies should report donor criteria, screening tests, stool handling time, processing method, storage conditions, microbial dose or a justified proxy, viability data where available, route of administration, dosing frequency, recipient diet, concurrent medications, adverse-event grading, and microbiome endpoints. The GRAFT framework for animal fecal transplantation reporting provides useful principles, although companion-animal-specific extensions may be needed [125].
Because dogs and cats live in close contact with humans, FMT also has a One Health dimension. Donor material should be screened not only to protect the recipient, but also to reduce risks of zoonotic pathogen transmission and antimicrobial-resistance dissemination within households and veterinary environments [98,104]. Responsible clinical translation will therefore require not only efficacy trials, but also standardized reporting, traceable donor screening, long-term safety monitoring, and species-specific guidance for routine veterinary use.
10. Limitations of This Review
This review used a structured narrative approach rather than a registered systematic review. Accordingly, no formal risk-of-bias assessment, PRISMA flow diagram, exhaustive search-yield count, or meta-analysis was performed. The synthesis may therefore be influenced by publication bias, selective reporting, and the narrative interpretation of heterogeneous study designs, populations, protocols, and outcome measures. In addition, some recent studies were preliminary in design or had limited follow-up, which restricts conclusions about durability of response and long-term safety. The literature search was limited to PubMed/MEDLINE, PubMed Central, and Web of Science, and independent duplicate screening and data extraction were not performed, which may have increased the potential for subjective study selection or omission of relevant evidence. In addition, limited non-peer-reviewed data were used where relevant, and the substantial heterogeneity in study populations, FMT protocols, outcome measures, and follow-up further limits comparability across studies. Diagnostic characterization also differed among canine CE studies, and histopathological confirmation of intestinal inflammation was not consistently performed or required, limiting direct comparison of broader CE populations with histopathologically confirmed CIE cohorts. Collectively, these limitations reduce confidence in conclusions regarding clinical efficacy, long-term safety, proposed mechanisms, and the appropriate clinical use of FMT.
11. Conclusions
FMT is a biologically plausible and increasingly standardized microbiome-directed intervention for companion animals. In dogs, the strongest clinical evidence supports cautious investigation and selected case-by-case adjunctive use in CE, as well as in specific acute infectious settings, particularly canine parvoviral enteritis. However, most canine CE evidence remains observational, underpowered, or confounded by concurrent therapy, and the available studies include heterogeneous disease phenotypes and diagnostic criteria, with histopathological confirmation of intestinal inflammation not consistently available. Definitive efficacy beyond spontaneous remission, contextual effects, and standard treatment has therefore not yet been established. In cats, FMT appears generally well tolerated in the short term, but evidence for clinical efficacy remains unproven. The lack of significant improvement in primary endpoints in the first controlled feline chronic enteropathy trial should temper clinical claims while motivating better-designed studies using repeated dosing, route comparisons, phenotype stratification, and longer safety follow-up.
Mechanistic understanding supports a multi-level model involving microbial engraftment, metabolic restoration, immune modulation, and gut–brain or gut–skin axis signaling, but veterinary-specific validation remains limited. The next phase of the field should prioritize adequately powered sham-controlled trials, standardized product preparation, rigorous donor screening, dose-finding studies, long-term safety surveillance, and harmonized reporting standards. With these safeguards, FMT may become an important adjunct in the veterinary management of microbiome-associated disease; current evidence supports careful, evidence-generating implementation rather than unrestricted routine use or routine first-line use.
Acknowledgments
During the preparation of this manuscript, the authors used ChatGPT (GPT-4o, OpenAI) to assist with linguistic editing to improve clarity and readability, as well as with the drafting of conceptual schematic figures. All AI-assisted material was critically reviewed, edited, and verified by the authors for scientific accuracy, and the authors take full responsibility for the final content of this publication.
Author Contributions
Conceptualization, J.J. and W.B.; methodology, J.J. and C.X.; literature search and data extraction, J.J. and C.X.; writing—original draft preparation, J.J.; writing—review and editing, J.J. and W.B.; supervision, W.B. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
No new data were created or analyzed in this study. Data sharing is not applicable to this article.
Conflicts of Interest
The authors declare no conflicts of interest.
Funding Statement
This research received no external funding.
Footnotes
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References
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Associated Data
Data Availability Statement
No new data were created or analyzed in this study. Data sharing is not applicable to this article.