**Background:** The gut microbiota plays a crucial role in integrating the neural, endocrine, and immune systems via the gut-brain-immune axis. In humans, dysbiosis has been linked to mental health disorders including depression, anxiety, bipolar disorder, and schizophrenia. However, research on the association between gut microbiota and behavioral issues in production, performance, and companion animals is limited. This systematic review provides the first compilation of current progress in gut microbiota analysis across pigs, horses, and dogs, comparing findings to human mental health literature.
**Methods:** This systematic review adhered to the PRISMA framework. A systematic search was conducted in PubMed from 1 August to 30 September 2022 using species-specific search terms for porcine, equine, and canine studies, combined with (microbiota OR microbiome) AND (gut OR gastrointestinal OR "gut-brain") AND (behaviour OR behavioural OR stereotypies). Inclusion criteria required relevance to the research topic, publication in English, peer-reviewed full-text availability, and publication within the last 10 years. A separate search for human meta-analyses and systematic reviews published since 2020 was also conducted. A total of 372 articles were initially identified; after screening, 39 studies met inclusion criteria (5 in pigs, 11 in horses, 9 in dogs, and 14 in human patients with mental disorders).
**Key Results:** Across all species, no significant differences in alpha diversity (within-sample richness) were found between behaviorally affected animals and controls, but consistent differences in beta diversity (between-sample variability) were observed. In humans with mental disorders, the gut microbiome consistently displayed an enrichment of pro-inflammatory and lactic acid-producing bacteria (e.g., Lactobacillus, Streptococcus, Enterococcus, Bifidobacterium) and a reduction in butyrate-producing bacteria (e.g., Coprococcus, Faecalibacterium, Roseburia). In pigs, tail-biters showed increased Firmicutes (Clostridiales, Lachnospiraceae, Ruminococcaceae) and decreased Lactobacillus, while tail-bitten victims showed increased Sphaerochaeta, Blautia, and Alistipes. In horses, high-starch diets were linked to decreased Ruminococcaceae and increased Streptococcus, with abnormal behaviors including oral stereotypies (24.2% microbiability), locomotion stereotypies (16.2%), aggressiveness (13%), and hypervigilance (9%). In dogs, phobic dogs showed enrichment of Lactobacillus, while aggressive dogs showed elevated Firmicutes and reduced Bacteroides. Cross-species comparisons revealed that population shifts in Firmicutes, particularly Clostridiaceae, Lachnospiraceae, Oscillospiraceae, and Lactobacillaceae, showed the strongest association with behavioral and mental disorders across all species.
**Clinical Implications:** This review establishes that an association exists between gut microbiota diversity and abnormal behavioral phenotypes across pigs, dogs, and horses, with similar microbiota population changes evident in human mental health patients. However, insufficient data exist to identify this association as causal. The findings provide testable hypotheses for future research to establish causal relationships and offer potential for novel therapeutic interventions (e.g., probiotics, prebiotics, SCFA supplementation, dietary modifications) aimed at restoring a healthy gut-brain-immune axis to mitigate behavioral issues and improve health, performance, and production in animals. Limitations include the use of partial 16S rRNA gene sequencing, small sample sizes, and the focus on bacterial components only, excluding fungi and bacteriophages.