与犬猫相关的非幽门螺杆菌属螺旋杆菌物种在人类感染中的人兽共患潜力：一项系统综述。 机翻

Abstract

Background

Non–Helicobacter pylori Helicobacter (NHPH) spp. are clinically relevant organisms found in humans and several animal hosts. Dogs and cats are natural hosts of multiple gastric and enterohepatic NHPH spp. and may represent potential sources of human exposure.

Objective

This systematic review aimed to synthesize the clinical, epidemiological, and molecular evidence concerning human infections involving dog‐ and cat‐associated NHPH spp. and to evaluate the evidence for a possible epidemiological association with companion animals.

Methods

PubMed and Scopus databases were searched for studies published from 2000 through the final search on April 15, 2026. Eligible studies reported human infection with NHPH spp. involving H. heilmannii sensu stricto (s.s), H. felis, H. bizzozeronii, H. salomonis, or H. canis. The following information was extracted: study and patient characteristics, NHPH species, human samples, diagnostic techniques, molecular confirmation, immunological state, clinical results, and exposure to dogs and/or cats. The risk of bias was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist appropriate for each study design.

Results

Of 350 records identified, 51 studies met the inclusion criteria. The evidence consisted predominantly of case reports. H. heilmannii–related organisms were the most frequently reported, followed by H. canis, H. felis, H. bizzozeronii, and H. salomonis. Gastric NHPH infections were predominantly associated with gastric disease, while H. canis was mainly associated with systemic and extragastric infections, especially in immunocompromised or clinically vulnerable patients. Molecular confirmation was reported in 66.7% of studies (34/51), with one additional study providing molecular confirmation for only 2 of 22 cases. Dog and/or cat exposure was documented in 41.2% of studies (21/51). Although several studies identified the same NHPH spp. in humans and companion animals, paired strain‐level molecular evidence remained limited and was insufficient to establish the direction of transmission.

Conclusion

Numerous gastrointestinal and systemic infections in humans have been linked to NHPH spp. found in dogs and cats. According to available data, dogs and cats may act as reservoirs or sources of human NHPH infection, given the recognized zoonotic potential of these pathogens. However, direct animal‐to‐human transmission and its direction have not been conclusively established. This is largely due to the limited availability of strain‐level molecular comparisons and paired human–animal sampling. To clarify transmission routes and improve integrated One Health surveillance, consistent molecular identification and comparative genomic studies are therefore required.

Keywords: companion animals, Helicobacter bizzozeronii, Helicobacter canis, Helicobacter felis, Helicobacter heilmannii, Helicobacter salomonis, non–Helicobacter pylori helicobacter, One Health

1. Introduction

Helicobacter spp. are Gram‐negative, spiral or curved, microaerophilic bacteria that colonize the gastrointestinal tract of humans and a wide variety of animal species. In addition to the human‐adapted Helicobacter pylori, several non–H. pylori Helicobacter (NHPH) spp. are increasingly recognized as clinically relevant in human and veterinary medicine. Historically, long spiral organisms observed in gastric tissues were collectively described as Helicobacter‐like organisms, H. heilmannii–like organisms, or H. heilmannii sensu lato (s.l.), because morphology alone did not permit reliable species‐level differentiation. Subsequent molecular investigations demonstrated that these organisms represent several distinct Helicobacter spp., leading to more precise species‐level classification and to the distinction between H. heilmannii sensu lato (s.l.) and H. heilmannii sensu stricto (s.s.) [1, 2]. NHPH spp. are broadly classified according to tissue tropism into gastric helicobacters, which colonize the stomach and include H. felis, H. heilmannii s.s., H. salomonis, and H. bizzozeronii, and enterohepatic helicobacters, which primarily inhabit the intestinal or hepatobiliary tract and include H. bilis and H. canis [3, 4].

Dogs and cats are important reservoirs of several gastric and enterohepatic NHPH spp. and may represent sources of human exposure. H. heilmannii s.s. and H. felis have been detected in both cats and dogs, whereas H. bizzozeronii and H. salomonis are predominantly associated with dogs. H. canis has also been detected in both dogs and cats. These animals may remain asymptomatically colonized, and transmission to humans may occur through direct or indirect contact with these animals; however, the specific transmission pathways and direction of transmission remain uncertain [1, 5, 6].

Human infections involving gastric NHPH spp. have been associated with chronic gastritis, dyspepsia, peptic ulcer disease, and gastric mucosa‐associated lymphoid tissue (MALT) lymphoma. In contrast, H. canis has primarily been associated with extragastric manifestations, such as bacteremia, cellulitis, hepatitis, and cholecystitis, particularly in immunocompromised patients [7–9].

The accurate identification of NHPH spp. remains challenging. Histopathological examination can detect long spiral organisms in gastric tissue but cannot reliably differentiate closely related NHPH spp. Culture is also difficult because many NHPH spp. are fastidious and require specialized growth conditions. Molecular methods, including species‐specific PCR, fluorescence in situ hybridization, and sequencing of targets such as the 16S rRNA, 23S rRNA, and ureAB genes, have improved species‐level identification [10–13]. More recent applications of next‐generation sequencing and whole‐genome sequencing have provided greater taxonomic resolution and revealed previously unrecognized diversity among gastric Helicobacter spp. from human and animal hosts [14, 15]. However, strain‐level genomic comparisons of epidemiologically linked humans and companion animals remain limited.

Previous reviews have broadly addressed the pathogenic and zoonotic significance of NHPH spp. in humans and animals [1, 5, 7, 9]. However, a systematic synthesis specifically focusing on documented human infections involving dog‐ and cat‐associated NHPH spp. remains limited, particularly with regard to species distribution, clinical manifestations, molecular identification, patient immune status, companion‐animal exposure, and evidence of possible zoonotic associations. Therefore, this systematic review aimed to synthesize the available clinical, epidemiological, and molecular evidence on human infections involving dog‐ and cat‐associated NHPH, specifically H. heilmannii s.s., H. felis, H. bizzozeronii, H. salomonis, and H. canis, and to evaluate the epidemiological evidence for a possible association with exposure to dogs and cats from a One Health perspective.

2. Materials and Methods

2.1. International Prospective Register of Systematic Reviews (PROSPERO) Registration and Reporting Guidelines

The review protocol was registered in the PROSPERO (CRD420261309381).

2.2. Information Sources and Search Strategy

A comprehensive literature search was conducted in PubMed and Scopus between February 15, 2026, and April 15, 2026, to identify eligible studies published from 2000 through the final search date of April 15, 2026. The same combination of keywords and Boolean operators was applied in both databases: (“Non‐Helicobacter pylori Helicobacter” OR NHPH OR “Helicobacter felis” OR “Helicobacter heilmannii” OR “Helicobacter bizzozeronii” OR “Helicobacter salomonis” OR “Helicobacter canis”) AND (human OR patient OR infection) AND (dog OR cat OR companion animal OR pet OR zoonotic). Only publications written in English were included. To identify potentially eligible studies not retrieved by the initial search, additional searches were conducted in PubMed and Scopus using broader combinations of relevant search terms. Eligible publication types included full‐text articles, case reports, case series, observational studies, and published abstracts that provided sufficient information for eligibility assessment and data extraction. The literature search was limited to PubMed and Scopus databases because access to other subscription‐based databases, including Web of Science and Embase, was unavailable.

2.3. Study Design and Selection

This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 guidelines [16]. All records retrieved from PubMed and Scopus were imported into Rayyan, a web‐based platform for systematic review screening [17]. Rayyan was used to identify and remove duplicate records and to manage title and abstract screening and full‐text eligibility assessment. One reviewer screened all records, assessed the available informative reports according to the eligibility criteria, and performed data extraction and methodological quality assessment. The study selection process was documented using a PRISMA 2020 flow diagram. ChatGPT (OpenAI) was used as an assistive tool for structuring the literature review and extracting study data; the extracted data were then reviewed and verified by the author.

2.4. Inclusion and Exclusion Criteria

2.4.1. Inclusion Criteria

2.4.2. Exclusion Criteria

2.5. Data Extraction and Classification

2.6. Risk‐of‐Bias Assessment

The quality of the included studies was evaluated by the reviewer using the JBI critical appraisal checklist appropriate to each study design [18]. Each appraisal item was rated as “Yes,” “No,” “Unclear,” or “Not applicable.” An “Unclear” rating was assigned when the available information was insufficient to make a judgment, particularly for publications available only as abstracts.

2.7. Data Synthesis and Statistical Analysis

The findings were synthesized narratively and presented in structured tables. Comparable data were summarized using frequencies and percentages. No inferential statistical analysis was performed. Meta‐analysis was not conducted because of heterogeneity in study designs, participant characteristics, diagnostic methods, and reported outcomes.

3. Results

A total of 350 records were identified, of which 51 studies were included in this systematic review (Figure 1; Table 1). The included studies were published between 2000 and 2026. The included studies represented five geographical regions, with the largest proportion originating from Europe (24/51, 47.1%), followed by Asia (15/51, 29.4%), North America (9/51, 17.6%), Africa (2/51, 3.9%), and Oceania (1/51, 2.0%).

[图：PRISMA 2020 flow diagram showing the identification, screening, eligibility assessment, and inclusion of studies in the ]

The included studies comprised case reports, case series, prevalence studies, cross‐sectional studies, and molecular investigations. Both adult and pediatric populations were represented. The studies reported human infections involving the gastric NHPH spp. H. heilmannii s.s., H. felis, H. bizzozeronii, and H. salomonis, as well as the enterohepatic sp. H. canis. The characteristics of the included studies, including study design, human population, NHPH spp., sample type, diagnostic method, molecular confirmation, patient characteristics, immune status, clinical findings or outcomes, and animal exposure are summarized in Table 1.

Most of the included studies focused on gastric NHPHs, whereas H. canis was reported mainly in case reports of extragastric infections. Among the gastric NHPHs, H. heilmannii and H. heilmannii–like organisms were the most frequently reported, followed by H. felis, H. bizzozeronii, and H. salomonis. However, several studies relied primarily on bacterial morphology and reported H. heilmannii–like organisms without definitive species‐level identification. Molecular studies identified single or mixed infections involving two or more Helicobacter spp. [11–13, 30, 56]. Gastric biopsy specimens obtained during upper gastrointestinal endoscopy were the primary samples used to detect gastric NHPHs. Histopathology, immunohistochemistry, PCR, and nucleotide sequencing were used either individually or in combination. Molecular confirmation using PCR and/or nucleotide sequencing was reported in 34 of the 51 included studies (66.7%). In one additional study, PCR was performed in only 2 of 22 cases and was therefore classified as partial molecular confirmation. Blood cultures followed by molecular identification were used mainly in reports of systemic H. canis infection. Other samples evaluated in a smaller number of studies included saliva, buccal swabs, and stool specimens.

Clinical manifestations associated with gastric NHPH infections (H. heilmannii, H. felis, and H. bizzozeronii) included chronic or chronic‐active gastritis, dyspepsia, abdominal discomfort, nausea, vomiting, peptic or gastric ulcers, and gastric MALT lymphoma [26, 30, 31, 46, 47, 53, 60, 61, 63]. H. canis was mainly associated with extragastric and systemic infections, including bacteremia, recurrent fever, and cellulitis. Many of these infections were reported in immunocompromised or clinically vulnerable patients [21, 25, 29, 33, 36, 50, 55]. Similar clinical manifestations were also reported in pediatric patients [36, 48, 49, 60, 61].

In histopathological examinations, gastric NHPH infections were mainly characterized by chronic or chronic‐active gastritis with mononuclear inflammatory cell infiltration and varying degrees of neutrophilic activity [26, 46, 47, 53, 61, 63]. The organisms were frequently detected in the gastric mucus layer, within the foveolae, or in glandular lumina [26, 46, 47, 57]. In children, histological evidence of gastritis was also observed despite normal or nonspecific endoscopic findings [60, 61]. Yakoob et al. [63] reported intestinal metaplasia in 25% (2/8) of patients coinfected with H. pylori and H. heilmannii and in 20% (1/5) of those coinfected with H. pylori and H. felis, compared with 3% (3/94) of patients infected with H. pylori alone. Gastric MALT lymphoma was also reported in association with H. heilmannii infection [31, 46, 47]. Kamio et al. [19] reported H. heilmannii–associated gastritis characterized by predominant lymphocytic infiltration and relatively low neutrophilic activity in a patient with multiple synchronous early gastric cancers.

Among the 51 included studies, 21 (41.2%) documented current, previous, or possible exposure to dogs and/or cats. These studies included case reports, pediatric case series, and observational studies [8, 19–26, 33, 36, 47, 50–52, 54, 55, 59, 61, 63, 64]. However, information on companion‐animal exposure was unavailable in many of the included studies. Several studies also investigated NHPH spp. in both humans and companion animals [11, 51, 59, 64]. Van den Bulck et al. [11] detected several gastric NHPH spp. in human, dog, and cat populations. De Bock et al. [51] detected H. felis in both a patient and her pet dog. Chung et al. [59] detected H. felis and H. bizzozeronii in humans and dogs and reported an association between dog contact and human H. felis infection. Moussa et al. [64] detected H. heilmannii in humans, dogs, and cats, whereas H. felis was not detected.

3.1. Risk‐of‐Bias Assessment

The risk of bias of all 51 included studies was evaluated using the JBI critical appraisal checklist appropriate to each study design, including 29 case reports, six case series, eight analytical cross‐sectional studies, seven prevalence studies, and one mixed observational/cohort study. Overall, full‐text case reports provided adequate clinical and diagnostic information, although reporting of adverse events, follow‐up, immune status, and animal exposure was inconsistent. The main limitations of case series were unclear case inclusion and recruitment methods, while cross‐sectional studies had insufficient control of confounding factors and, at times, unclear sampling methods. Prevalence studies were mainly limited by sampling frames, population representativeness, and insufficient justification of sample size. Species confirmation also varied, ranging from histopathological morphology to species‐specific PCR or sequencing. Nineteen publications were available only as sufficiently informative abstracts; therefore, items that could not be confirmed were rated as “Unclear” rather than “No.” No study was excluded solely based on the appraisal results (Tables S1–S5).

4. Discussion

Dogs and cats are natural hosts and potential reservoirs of several gastric NHPH spp., including H. heilmannii s.s., H. felis, H. bizzozeronii, and H. salomonis. These organisms commonly colonize the gastric mucosa of companion animals, frequently without evident clinical signs. The high colonization rates reported in dogs and cats, together with the detection of these animal‐associated NHPH spp. in human gastric specimens, support a possible zoonotic association [1, 5, 11, 12].

Gastric NHPH spp. predominated among the organisms reported in the included studies, particularly H. heilmannii and H. heilmannii–like organisms, followed by H. felis, H. bizzozeronii, and H. salomonis. Historically, long, tightly coiled gastric Helicobacter organisms were often classified collectively as H. heilmannii or H. heilmannii–like organisms based on histopathological morphology. However, several gastric NHPH spp. are morphologically similar and cannot be reliably differentiated by routine microscopy. The subsequent use of species‐specific PCR, sequencing, and fluorescence in situ hybridization enabled more accurate species‐level identification [10–13]. Therefore, although H. heilmannii–related organisms were the most frequently reported in this review, historical diagnostic grouping may have influenced the reported distribution of individual gastric NHPH spp.

The clinical patterns identified in this review differed according to NHPH spp. Gastric NHPH spp. were predominantly associated with inflammatory and ulcerative gastric diseases, including chronic or chronic‐active gastritis, dyspepsia, peptic or gastric ulceration, and, less frequently, gastric MALT lymphoma. This clinical pattern is consistent with the gastric colonization of these organisms. The clinical spectrum of gastric NHPH infection partially overlaps with that of H. pylori, emphasizing the importance of considering NHPH in patients with unexplained gastric disease, particularly when H. pylori is not detected [13, 46, 47, 61]. The reported association with gastric MALT lymphoma is clinically important, although the limited number of cases and variability in species identification preclude conclusions regarding species‐specific risk [31, 46, 47]. Similarly, occasional reports of gastric cancer in NHPH‐positive patients warrant further investigation but do not establish a causal relationship [19].

In contrast, H. canis showed a predominantly extragastric and systemic clinical profile, with much of the available evidence derived from individual case reports. Reported manifestations included bacteremia, recurrent fever, and cellulitis, with other invasive infections also described. This difference is consistent with the distinct biological characteristics and tissue tropism of H. canis as an enterohepatic rather than a gastric Helicobacter species [3, 8]. Many invasive H. canis infections occurred in immunocompromised or clinically vulnerable patients, including individuals with hypogammaglobulinemia, malignancy, transplantation, or immunosuppressive therapy [21, 25, 29, 33, 55]. This pattern suggests that impaired host defenses may facilitate bloodstream invasion and systemic disease. However, H. canis infection has also been reported in patients without recognized severe immunosuppression, indicating that immune status alone does not explain susceptibility [50].

Dogs and cats commonly harbor gastric NHPH spp. and may remain asymptomatically colonized. Some of these organisms have also been detected in the oral cavity and saliva of companion animals. Close contact with colonized companion animals, including exposure to saliva or vomitus, represents a biologically plausible route of NHPH transmission. Exposure to fecal material and indirect environmental contamination has also been proposed; however, the relative importance of these potential routes remains uncertain [1, 22].

Documented dog and/or cat exposure in a substantial proportion of the included literature, together with reports of the same Helicobacter spp. in humans and companion animals, provides epidemiological support for a possible zoonotic association. In particular, the associations reported between continuous dog contact and human H. felis and H. bizzozeronii infections strengthen the epidemiological plausibility of companion‐animal exposure [59]. Nevertheless, species‐level concordance between humans and animals does not equate to evidence of transmission. Establishing zoonotic transmission requires stronger epidemiological linkage and strain‐level molecular or genomic comparison.

Furthermore, dog‐ and cat‐associated NHPH spp. have been identified in patients without documented companion‐animal contact [10, 12, 48], suggesting that unrecognized previous contact, other animal reservoirs, or indirect environmental exposure may also contribute. Thus, the current evidence supports the zoonotic potential of dog‐ and cat‐associated NHPH but does not establish direct or exclusive animal‐to‐human transmission.

The geographical distribution of the available evidence also warrants careful interpretation. The predominance of studies from Europe (47.1%) and Asia (29.4%), compared with the limited evidence from North America, Africa, and Oceania, may reflect differences in clinical awareness, access to endoscopy and molecular diagnostic methods, research capacity, and publication practices rather than true geographical differences in NHPH occurrence. Consequently, the available evidence does not permit reliable comparisons of regional incidence or prevalence. This geographical imbalance highlights the need for further studies in underrepresented regions using standardized diagnostic and epidemiological approaches.

From a One Health perspective, the detection of related NHPH spp. in both humans and companion animals highlights the importance of integrating human, veterinary, and molecular investigations. Future studies should include standardized species‐level identification, systematic assessment of animal exposure, paired sampling of patients and their companion animals, and detailed genomic comparisons. Such approaches would help distinguish simple host sharing of the same NHPH spp. from epidemiologically linked infections, providing stronger evidence of strain relatedness and possible transmission pathways. Integrated human–animal surveillance, together with evidence‐based education of pet owners regarding routine hygiene during close contact with companion animals, may also be considered within a One Health framework, although specific preventive measures require stronger evidence regarding transmission routes. The overall evidence should also be interpreted in light of its methodological limitations. The predominance of case reports, case series, and relatively small observational studies provides valuable information on uncommon clinical presentations and generates hypotheses regarding zoonotic exposure, but offers limited evidence for population‐level risk or causal transmission relationships. Similarly, insufficient consideration of potential confounding factors in several analytical studies limits the interpretation of associations between companion‐animal exposure and human infection. Consequently, the available evidence supports zoonotic potential and suggests a possible epidemiological association, while stronger prospective and molecular epidemiological studies are required before direct animal‐to‐human transmission can be established.

5. Limitations

This review has several limitations that should be considered when interpreting its findings. Most of the available evidence was derived from case reports, case series, and small observational studies. Consequently, the current evidence provides limited support for causal inference, assessment of risk factors, or reliable estimation of population prevalence. Considerable heterogeneity was also observed across studies in terms of study design, patient characteristics, diagnostic approaches, and reported outcomes, precluding quantitative pooling and meta‐analysis. Nineteen publications were available only as sufficiently informative abstracts and contained adequate information for eligibility assessment and data extraction. Nevertheless, the absence of full‐text reports prevented complete verification of methodological details and resulted in a greater number of “Unclear” judgments during critical appraisal. Diagnostic approaches were also inconsistent across studies. In particular, some reports identified gastric NHPH based on histopathological morphology without molecular confirmation at the species level, which may have affected the accurate differentiation of morphologically similar gastric NHPH spp. Information regarding exposure to dogs and cats was not consistently reported, while paired sampling of patients and their companion animals was uncommon. Furthermore, strain‐level genomic comparisons were rarely performed. Therefore, the detection of the same NHPH spp. in humans and companion animals could not distinguish direct transmission from exposure to a shared source or independent acquisition. The direction of any potential transmission also remains unresolved. Study selection, data extraction, and methodological quality assessment were undertaken by a single reviewer, introducing the possibility of selection bias and subjective judgment. In addition, the search was restricted to PubMed and Scopus and to peer‐reviewed publications in English. Relevant evidence indexed exclusively in other databases or published in other languages may therefore have been missed. Publication bias should also be considered because unusual or clinically important NHPH infections may be more likely to appear in the published literature than uncomplicated or asymptomatic infections. Finally, the geographical concentration of studies in Europe and Asia limits the generalizability of the findings to underrepresented regions.

6. Conclusion

This systematic review synthesized the available evidence on human infections involving dog‐ and cat‐associated NHPH spp., particularly H. heilmannii s.s., H. felis, H. bizzozeronii, H. salomonis, and H. canis. These organisms have been reported across a spectrum of gastric and systemic infections in humans. The available evidence supports their zoonotic potential and suggests a possible epidemiological association with companion‐animal exposure; however, direct animal‐to‐human transmission has not been conclusively established. Further studies incorporating systematic exposure assessment, paired sampling of humans and their companion animals, and strain‐level genomic comparisons are needed to clarify strain relatedness and potential transmission pathways. Integrating these approaches within a One Health framework may improve understanding of the epidemiology and public health significance of companion‐animal‐associated NHPH infections.

Funding

No funding was received for this research.

Disclosure

The author has read and approved the final version of the manuscript. The author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. The author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting Information

Additional supporting information can be found online in the Supporting Information section.

Supporting information

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Acknowledgments

The author used ChatGPT (OpenAI) as an assistive tool for language editing, drafting assistance, and manuscript formatting. All AI‐assisted content was thoroughly reviewed, verified, and revised by the author, who takes full responsibility for the scientific content, accuracy, and conclusions of the manuscript.

Al‐Gburi, Nagham Mohammed , Zoonotic Potential of Non–Helicobacter pylori Helicobacter Species Associated With Dogs and Cats in Human Infections: A Systematic Review, Veterinary Medicine International, 2026, 3012354, 13 pages, 2026. 10.1155/vmi/3012354

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Contributor Information

Nagham Mohammed Al-Gburi, Email: nagam22.vc22@covm.uobaghdad.edu.iq.

Lipi Buch, Email: lbuch@wiley.com.

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its Supporting Information files.

References

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Associated Data

Supplementary Materials

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Data Availability Statement

All data generated or analyzed during this study are included in this published article and its Supporting Information files.