The gut microbiome and health of companion animals: Insights into physiology, dysbiosis and disease association

Introduction

The gastrointestinal system, commonly referred to as the gut, serves as the primary organ responsible for acquiring nutrients and essential compounds required to sustain the host's physiological functions. Health of animals is highly influenced by the multidirectional interaction between the gut microbiome and various organ systems (Rindels JE and Loman BR., 2024) [1] . Maintaining a healthy gut is fundamental to the proper functioning of the body on a daily basis. This system does not rely exclusively on the host's digestive enzymes; rather, it depends significantly on activity of the microbiota to digest and metabolize compounds that host alone cannot efficiently process. This symbiotic relationship plays a critical role in maintaining intestinal health, which in turn has a profound impact on the overall well-being of the host. Despite its importance, the hostmicrobe interaction is frequently underestimated and insufficiently addressed, especially in pets.

"A healthy gut reflects a healthy pet".

Physiology of gut microbiome

The term gut microbiome refers to the collection of microbes that reside in the gastrointestinal tract. It includes bacteria, viruses, bacteriophages, protozoa, and fungi and forms an integral part of host metabolism (Belkaid Y and Hand TW, 2014) [2] . These gut microbes maintain a positive and balanced (symbiotic) relationship with host's gut. However, microbial composition and abundance were influenced by various factors such as age, nutritional status, type of feed, management practices, concurrent diseases, hormonal changes, medications, and stress, all of which can alter their population. Due to these varying factors, there is a considerable variation in gut microbiota not only between species but also among individual animals.

Each animal possesses a unique gut microbiome profile. According to Li Q et al., 2017 [3] , canine models fed highprotein, low-carbohydrate (HP-LC) diets had lower Bacteroidetes/Firmicutes ratios and higher Bacteroides/Prevotella ratios compared to those fed lowprotein, high-carbohydrate (HC) diets. Additionally, the abundances of Clostridium hiranonis, Ruminococcus gnavus, and Clostridium perfringens were increased. This study demonstrates that even dietary variations can significantly influence the composition of the gut flora in pets. In neonates, microbial population is usually low. However, as the animal ages, the diversity and complexity of the microbial community increase. Exposure to environmental microbes facilitates the development of immunity, often indirectly. These microbes also act as a protective barrier by colonizing the gut and preventing the attachment and replication of pathogenic organisms. Function and composition of gut is shaped by competition and interactions among microbes (Machado D et al., 2021) [4] . Additionally, gut microbes secrete antimicrobial peptides that inhibit the growth of harmful organisms. Common antimicrobial peptides secreted in the gut include defensins, cryptdin-related peptides, and cathelicidins. Among these, defensins are most prominent (Marlon H. Cardoso et al., 2022) [5] . The breakdown of nutrients by gut microbes surpasses the capability of host's digestive enzymes. Moreover, these microbes contribute to the synthesis of several essential compounds, including vitamins and neurotransmitters (such as Serotonin). The majority of gut microbes colonize the gastrointestinal tract through ingesta; hence, nutrition has a vital role to play in shaping gut. Gut influenes metabolism and overall growth, both directly and indirectly. Directly it supports nutrient digestion and absorption, indirectly it modulates microbial products such as short-chain fatty acids (SCFAs), and influences gut-endocrine signalling via ghrelin-or leptin-mediated pathways, which in turn regulate growth hormone secretion. Loss of these commensal microbiota is associated with decreased SCFA and bile acids. Compounds like tryptophan from the gut play a significant role in daily metabolism, including inflammation, immune modulation, and the synthesis of serotonin.

Microbiome Population

Various species of bacteria (most predominant), archaea, fungi, protozoa, and viruses inhabits the gastrointestinal tract (GI) of cats and dogs (Suchodolski JS., 2011) [7] . According to Pilla R and Suchodolski JS., 2020 [8] , majority of bacterial population of canine gut comprises of Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria and Actinobacteria. These inhabitants of intestinal tract usually trillions in number may interact with one another and with the host through direct or indirect mechanisms (Wang S et al., 2023). Α-and β-diversity metrics are used to study gut microbial diversity, in which alpha denotes the diversity of microbes within a single sample or group, whereas beta compares the microbial composition between different groups or samples. The Bacterium count in ileum is approximately 10 7 CFU/g or ml and in colon of dogs and cats, it ranges between 10 9 and 10 11 CFU/g or ml of intestinal content. The bacterial groups that are predominantly cultured from intestines of dogs and cats are Bacteroides, Clostridium, Lactobacillus, Bifidobacterium spp and Enterobacteriaceae (Suchodolski JS., 2011) [7] . 16s rRNA sequencing can be used to identify the microorganisms and its divergence is measured in βdiversity.

According to a study by Foster ML et al., 2013, they identified a total of 5 phyla of fungus spp. from naturally defecated stools. Among these, more than half of dogs were found with Ascomycota and Basidiomycota (in both groups of diseased and healthy). The remaining phyla that are identified were Chytridiomycota, Neocallimastigomycota and Microsporidia. Shi Y et al., 2021 [12] in their meta-analysis, concluded that dogs have a gut viral population comprising a total of 31 DNA and 32 RNA virus families. It includes population homologous to the animal viruses of family Astroviridae, Coronaviridae, phages of the family Microviridae, Siphoviridae and unclassified phages etc. These two studies reflect the high variability present in the gut microbiome.

Role of the Gut in Immunity

In the development of the host immune system, gut has an important role to play (Belkaid Y and Hand TW, 2014) [2] . Various pathogens through the ingesta enters the body, which in turn primes the host's adaptive immunity (T and B cells). The gut microbiome can enhance the host's non-specific immunity by maintaining and strengthening the intestinal barrier function. Mucus production is also pivotal for host defense, as it forms a physical barrier that separates bacteria from the host and avoids breach of the intestinal barrier (Takiishi T et al., 2017) [14] . Mucoprotein (MUC2) is the most abundant mucin in the gut and is found in the outer mucus layer. It competes with pathogenic bacteria to bind to the surface receptor, thereby inhibiting pathogen colonization. Antigens encountered at the gut epithelium help stimulate both local and systemic immune responses, particularly through the activation of enteric immune mechanisms. The development, growth and immune system activity is influenced and regulated by complex interaction between intestinal cell lining, residing microbiota and its metabolites (Soderholm AT and Pedicord VA, 2019) [15] . The host's response to both foreign and symbiotic microbes is essential for maintaining homeostasis, with Toll-like receptors (TLRs) playing a key role. Various metabolites that are metabolized by the microbiota are capable of communicating between immune cells and the gut epithelium (Ullah H et al., 2024) [16] . Lipopolysaccharides of bacterial cell wall mainly gram negative, is recognised by Toll-like receptor 4 (TLR4), which in turn activates the downstream antibacterial signalling pathways (Meghali Nighot et al., 2019) [17] . In neonates, establishment of intestinal immune defence, its maturation and homeostasis is influenced by early microbiota colonization (Takiishi T et al., 2017) [14] . Gut metabolites such as short-chain fatty acids (has anti-inflammatory activity), lysozymes, secondary bile acids, and antimicrobial peptides, can kill pathogenic bacteria. Additionally, for maintaining immune tolerance to commensal bacteria in alimentary tract intestinal lymphoid tissue termed as Gutassociated lymphoid tissue (GALT), plays a critical role (Ullah H et al., 2024) [16] .

Gut-Brain Axis

The two-way communication between central nervous system and microbiome of gut occurs via a network called gut-brain axis (GBA), this complex signalling pathway (nervous, immune, endocrine and metabolite(s)-mediated) regulates behaviour and cognition of host (E. Salvo-Romero et al., 2020), hence enteric nervous system is often termed as second brain of body (Kiełbik and Piłaszewicz et al., 2024) [19] . Vagal tone is highly affected by stress; as a potential stress stimulus can disrupts the tone of vagus nerve (part of cholinergic antiinflammatory system) and have negative impact on health of the intestine and its microbial composition (Bonaz B et al., 2018 and Sacoor C et al., 2024) [20,21] . The level of neurotransmitters such as norepinephrine, serotonin, GABA and dopamine is regulated by microbiome which in turn effect the neuronal operations and impacts the mental health (Gonçalves S et al., 2022 and Sacoor C et al., 2024) [22,21] . Mood, sleep, behaviours such as anxiety, interactions is chiefly regulated by Serotonin (Berger M et al., 2009; Kiełbik and Piłaszewicz et al., 2024) [23,19] . In humans, major part of dopamine synthesized in intestine and microbiota greatly influence its synthesis (Eisenhofer G et al., 1997; Kiełbik and Piłaszewicz et al., 2024) [24,19] . In animals, dopamine is involved in behaviour and learning, and also plays important roles in attention, cognition, and executive functions ( [25,26] .

Microbial dysbiosis

Immunoglobulin A (local secretory Ig), stomach acid (HCL), bile and other intestinal secretions, along with the continuous movement of gut (peristalsis), valves (illeo-caecal) are part of an inbuilt defence system that regulates and prevents microbial overgrowth in the gut (Sorathia SJ et al., 2025) [27] . When these mechanisms fail, dysbiosis can occur. Dysbiosis refers to significant disturbances in the population, composition, and functional activity of the gut microbiome. It is generally categorized into 3 types: (a) decreased beneficial microbes, (b) increased pathogenic organisms, and (c) a lack of diversity in microbial species (MM Roshan et al., 2022) [28] . A wide range of factors may contribute to dysbiosis, including age, enteral or extra-enteral infections, and secondary dysbiosis associated with primary dysfunction of organs such as the pancreas. Additional contributing factors include nutritional profile (particularly the type and quality of nutrients), exposure to acute or chronic toxins and chemicals, drug administration (especially antibiotics), hygiene practices, and environmental conditions. The disruption of the gut microbiota ecosystem can have far-reaching consequences. These effects can be broadly divided into: (1) Gut barrier disruption and (2) host immune and metabolic systems imbalances (Llorente C and Schnabl B., 2015; Hrncir T., 2022) [29,30] . Dysbiosis can both result from and contribute to intestinal inflammation. It has been associated with a greater risk of several conditions, including cancer, obesity, and inflammatory bowel diseases (IBD), especially due to cytokine imbalance (both pro-inflammatory and antiinflammatory cytokines) in humans. It occurs due to changes in normal population and colonization of disease promoting organisms (Ronald Tyszkowski and Raman Mehrzad, 2023) [31] . Although dysbiosis can occur due to a range of underlying causes, it is notably observed in certain diseases, such as exocrine pancreatic insufficiency. Disruption of the gut microbiome adversely affects intestinal function, compromises mucosal barrier integrity, and disturbs gut homeostasis, with potential systemic implications. Silvestrino M et al., 2025 [32] reported that dysbiosis has been linked to neuro-inflammatory and neuro-degenerative conditions, including epilepsy in dogs. This microbial imbalance can also lead to inflammation and altered expression of IFN-γ, TNF-α etc., which has been well studied in humans. In some cases, the disturbance is characterized not by a change in the overall microbial population but by alterations in microbial community composition such as the replacement of commensal anaerobes with facultative anaerobes and opportunistic pathogens like Clostridium difficile, which can markedly intensify dysbiosis.

Impact of Antimicrobials

It is essential to discuss antimicrobials whenever the gut microbiome is being discussed. Antimicrobials are doubleedged swords; they have a significant effect in controlling infections, but when used unregulated, they can have severe and deleterious effects on the body. Prolonged oral use of antimicrobials especially causes serious damage to the gut microbiome. These drugs are non-selective; they kill both symbiotic and pathogenic organisms, leading to gut dysbiosis. Rebuilding the damaged gut flora can take years, and in some cases, it may never fully return to its original state. The effects are particularly harmful in neonates and young animals, where the gut microbiome is still developing and maturing. Early disruption may result in persistent dysbiosis, even into adulthood. Moreover, antimicrobial abuse promotes antimicrobial resistance, allowing resistant organisms to colonize and potentially spread to other hosts, further disturbing their microbiomes. Therefore, the choice of antimicrobials including their type, dose, and duration should be carefully considered before prescribing.

Dysbiosis Index

The Dysbiosis Index (DI) is a validated quantitative qPCR assay and also assessable via metagenomic sequencing for fresh faecal samples (<12 hours) that quantifies the abundance of seven key bacterial taxa and summarizes the results as one single value, accurately predicting global shifts in the microbiome (Suchodolski JS., 2022; Sung CH et al., 2023) [33,34] . Al Shawaqfeh MK., 2017 reported a sensitivity of 74% and specificity of 95% for differentiating healthy dogs from those with chronic inflammatory enteropathies using the Dysbiosis Index. Suchodolski JS., 2022 [33] also noted that the DI can be used to assess the microbiome in clinical patients over time and in response to therapy (e.g., fecal microbiota transplantation). In cats, a panel of quantitative PCR (qPCR) assays was used by Sung CH et al., 2022 to measure the fecal abundance of total bacteria and seven bacterial taxa: Bacteroides, Bifidobacterium, Clostridium hiranonis, Escherichia coli, Faecalibacterium, Streptococcus, and Turicibacter. In contrast, Al Shawaqfeh MK et al., 2017 used a qPCR panel consisting of eight bacterial groups: total bacteria, Faecalibacterium, Turicibacter, Escherichia coli, Streptococcus, Blautia, Fusobacterium, and Clostridium hiranonis.

Diseases and Gut microbiome 9.1 Skin diseases

The gut is a strong immune regulator and when any changes occur, it affects various systems such as skin. In fact, their association is understudied, and only a few manifestations have been reported in various pathological conditions (O'Neill CA et al., 2016) [44] . A study on the skin and gut microbiota in canine atopic dermatitis conducted by Thomsen M et al., 2023 [45] concluded that in parallel with skin dysbiosis, there was also clear dysbiosis in the gut of atopic dogs and a decrease in the beneficial bacteria. In canids, high faecal concentrations of butyrate and propionate are positively correlated with the faecal abundance of Fusobacterium (Minamoto Y et al., 2019) [46] and it is also reported that in humans, significantly higher levels of butyrate and propionate showed decreased risk of atopy.

Enteric disorders

Inflammatory responses are often stimulated due to an increase in permeability to lipopolysaccharide, leading to chronic inflammation, which is the primary cause of overgrowth of microbes in human gut (Banaszak M et al., 2023) [47] . However, such reports are not yet well established in companion animals. There are only a few reports regarding changes in gut population associated with enteric disorders of dog and cat. Park JS et al., 2019 [48] reported that a decreased species richness of alpha diversity metrics was observed in dogs with canine parvoviral enteritis compared to healthy dogs. Nagahara T et al., 2023 [49] , conducted research on dogs with intestinal lymphangiectasia and healthy dogs. Their study revealed a decrease in intestinal bacterial diversity and butyrate-producing bacteria in affected dogs.

Chronic Kidney Disease (CKD)

In chronic kidney disease, severe changes in gut microbial composition are due to an increase in the luminal pH. Higher concentrations of ammonia, a microbial product of urea metabolism are found in intestinal lumen of affected patients either by diffusion, as a consequence of impairment to intestinal lining or through entero-hepatic cycle (Bourke E et al., 1966, ND Vaziri et al., 2012, Summers S and Quimby J., 2024) [50][51][52] . Ammonia (uremic toxin) accumulation, leads to disrupted profiles of essential compounds such as fatty acids and amino acids due to microbial dysmetabolism. This in turn promotes systemic inflammation and further impairs renal function (Summers S and Quimby J., 2024) [52] . Kim KR et al., 2023 [53] , from their study, concluded that the gut microbial population and composition may vary based on stage of CKD, observing a decrease in saccharolytic bacteria and an increase in proteolytic bacteria. These findings highlights the necessity of giving attention to gut health in management of CKD in dogs.

Exocrine Pancreatic Insufficiency (EPI)

In EPI, due to changes in pH, more available undigested nutrients in the gut, and a lack of pancreatic antimicrobial peptides (in pancreatic juice), there is severe faecal microbiota dysbiosis (restricted to the intestinal lumen [Anitha Isaiah et al., 2017]) [54] and SIBO, causing diarrhoea, toxin build-up in the gut, and also elevated serum folate levels (Vikram Chandu V et al., 2024) [55] .

Cardiac Disorders

There is limited data available regarding the correlation between cardiac disorders and gut dysbiosis. However, Li Q et al., 2021, studied the association between myxomatous mitral valve disease (MMVD) and gut-derived metabolites. They concluded that, there was an inverse association between Clostridium hiranonis (a gut bacteria important in converting bile acid) and MMVD. They also mentioned that the gut dysbiosis index increased in proportion to the severity of disease. In contrast, Seo J et al., 2020 [57] , reported that there was no significant change in microbiome diversity and richness in dogs with congestive heart failure. However, they did observe an increase in the abundance of Proteobacteria in the congestive heart failure study group.

Hepatobiliary disorders

The hepatobiliary system is a key part of the alimentary tract. A vast number of disorders affect it, which reflects the changes in gut homeostasis. Kummen M and Hov JR., 2019 [58] , reported that gut microbial dysbiosis was present in biliary biliary disorders such as primary biliary cholangitis and primary sclerosing cholangitis. These modifications may result from several mechanisms during chronic hepatobiliary disease (CHD); however, deeper alterations are due to cholestasis (Habermaass V et al., 2023) [59] . In cats, suspected of having hepatobiliary disease, bile sample do not contain a core microbiota and uncultured bacteria may contribute to the pathogenesis of the disease with bile E. coli bile infection.

Nervous disorders

A study by Silvestrino, M et al., 2025 [32] , concluded that epileptic dogs had reduced gut bacterial richness and uneven α-diversity compared to healthy controls, with no variations in β-diversity. Furthermore, their study observed a decrease in SCFA-producing bacteria, namely Faecalibacterium, Prevotella, and Blautia, and an increase in Escherichia coli, Clostridium perfringens, and Bacteroides in epileptic dogs. Although many studies have addressed the microbiota and its influence on anxiety disorders in humans and rodent models, there is a lack of insightful information on canine anxiety disorders (Sacoor C et al., 2024) [21] .

Gut Health and Cancer

The relationship between gut health and cancer development, while supported by limited data, is a growing area of research. The gut microbiome plays an important role in tumour initiation and progression, either by promoting inflammation, by altering microenvironment of tumour or by regulating the anti-cancer immune response. According to Breczko WJ et al., 2024 [62] , disruptions to this delicate balance can lead to chronic inflammation and a disturbed immune system. When these disruptions are combined with environmental and genetic factors, they may contribute to the development and progression of cancers, particularly of lymphatic system.

Conclusion

Studies on gut health in pets have expanded in recent years, leading to new discoveries, the development of novel treatment modalities, and support for maintaining optimal gut health in companion animals. However, while these mechanisms are well-documented in humans, data on similar interactions in dogs and cats remain limited. Although crossspecies insights offer a valuable theoretical framework, targeted research in canine and feline models is essential to deepen our understanding and improve clinical outcomes.

Conflict of Interest Not available

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References

1. Rindels JE, Loman BR. Gut microbiome, the key to our pets' health and happiness? Anim Front. 2024 Jun 20;14(3):46-53. DOI: 10.1093/af/vfae015. PMID:38910954; PMCID:PMC11188957.
2. Li Q, Lauber CL, Maulden CG, Pan Y, Hannah SS. Effects of the dietary protein and carbohydrate ratio on International Journal of Veterinary Sciences and Animal Husbandry https://www.veterinarypaper.com gut microbiomes in dogs of different body conditions. mBio. 2017;8:e01703-16. DOI: 10.1128/mBio.01703-16.
3. Machado D, Maistrenko OM, Andrejev S, Kim Y, Bork P, Patil KR. Polarization of microbial communities between competitive and cooperative metabolism. Nat Ecol Evol. 2021 Feb;5(2):195-203. DOI: 10.1038/s41559-020-01353-4. EPUB 2021 Jan 4. PMID:33398106; PMCID:PMC7610595.
4. Cardoso MH, Meneguetti BT, Oliveira NG Jr, Macedo MLR, Franco OL. Antimicrobial peptide production in response to gut microbiota imbalance. Peptides. 2022;157:170865. DOI: 10.1016/j.peptides.2022.170865.
5. Suchodolski JS. Diagnosis and interpretation of intestinal dysbiosis in dogs and cats. Vet J. 2016;215:30-7. DOI: 10.1016/j.tvjl.2016.04.011.
6. Suchodolski JS. Intestinal microbiota of dogs and cats: A bigger world than we thought. Vet Clin North Am Small Anim Pract. 2011 Mar;41(2):261-272. DOI: 10.1016/j.cvsm.2010.12.006. PMID: 21486635; PMCID:PMC7132526.
7. Pilla R, Suchodolski JS. The role of the canine gut microbiome and metabolome in health and gastrointestinal disease. Front Vet Sci. 2020 Jan 14;6:498. DOI: 10.3389/fvets.2019.00498. PMID: 31993446; PMCID:PMC6971114.
8. Wang S, Mu L, Yu C, He Y, Hu X, Jiao Y, et al. Microbial collaborations and conflicts: Unraveling interactions in the gut ecosystem. Gut Microbes. 2024;16(1):2296603. DOI: 10.1080/19490976.2023.2296603. Epub 2023 Dec 27. PMID:38149632; PMCID:PMC10761165.
9. Sarkar K, Sil PC. Effect of diet, pharmaceuticals, and environmental toxicants on gut microbiota imbalance and increased intestinal membrane permeability. In: Toxicological risk assessment and multi-system health impacts from exposure. Cambridge (MA): Academic Press; 2021, p. 403-13. DOI: 10.1016/B978-0-32385215-9.00007-6.
10. Foster ML, Dowd SE, Stephenson C, Steiner JM, Suchodolski JS. Characterization of the fungal microbiome (mycobiome) in fecal samples from dogs. Vet Med Int. 2013;2013:658373. DOI: 10.1155/2013/658373. EPUB 2013 Apr 23. PMID:23738233; PMCID:PMC3655676.
11. Shi Y, Tao J, Li B, Shen X, Cheng J, Liu H. The gut viral metagenome analysis of domestic dogs captures snapshot of viral diversity and potential risk of coronavirus. Front Vet Sci. 2021 Jul 7;8:695088. DOI: 10.3389/fvets.2021.695088. PMID: 34307533; PMCID:PMC8292670.
12. Xue J, Ajuwon KM, Fang R. Mechanistic insight into the gut microbiome and its interaction with host immunity and inflammation. Anim Nutr. 2020;6(4):421-428. DOI: 10.1016/j.aninu.2020.05.007.
13. Takiishi T, Fenero CIM, Câmara NOS. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers. 2017 Oct 2;5(4):e1373208, EPUB 2017 Sep 28, DOI: 10.1080/21688370.2017.1373208. PMID: 28956703; PMCID:PMC5788425.
14. Soderholm AT, Pedicord VA. Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity. Immunology. 2019 Dec;158(4):267-80. DOI: 10.1111/imm.13117. EPUB 2019 Oct 4. PMID: 31509239; PMCID: PMC6856932.
15. Ullah H, Arbab S, Tian Y, Chen Y, Liu CQ, Li Q, et al. Crosstalk between gut microbiota and host immune system and its response to traumatic injury. Front Immunol. 2024 Jul 31;15:1413485. DOI: 10.3389/fimmu.2024.1413485. PMID:39144142; PMCID:PMC11321976.
16. Nighot M, Rawat M, Al-Sadi R, Castillo EF, Nighot P, Ma TY. Lipopolysaccharide-induced increase in intestinal permeability is mediated by TAK-1 activation of IKK and MLCK/MYLK gene. Am J Pathol. 2019 Apr;189(4):797-812. DOI: 10.1016/j.ajpath.2018.12.016. PMID:30852046.
17. Romero SE, Stokes P, Gareau MG. Microbiota-immune interactions: From gut to brain. LymphoSign J. 2020;7(1):1-23. DOI: 10.14785/lymphosign-2019-0018.
18. Kiełbik P, Piłaszewicz WO. The relationship between canine behavioral disorders and gut microbiome and future therapeutic perspectives. Animals (Basel). 2024 Jul 12;14(14):2048. DOI: 10.3390/ani14142048. PMID:39061510; PMCID:PMC11273744.
19. Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Front Neurosci. 2018 Feb 7;12:49. DOI: 10.3389/fnins.2018.00049. PMID: 29467611; PMCID: PMC5808284.
20. Sacoor C, Marugg JD, Lima NR, Empadinhas N, Montezinho L. Gut-brain axis impact on canine anxiety disorders: New challenges for behavioral veterinary medicine. Vet Med Int. 2024 Jan 23;2024:2856759. DOI: 10.1155/2024/2856759. PMID:38292207; PMCID:PMC10827376.
21. Gonçalves S,Costa ND, Cardoso SM, Empadinhas N, Marugg JD. Enzyme promiscuity in serotonin biosynthesis, from bacteria to plants and humans. Front Microbiol. 2022;13:873555. DOI: 10.3389/fmicb.2022.873555.
22. Eisenhofer G, Aneman A, Friberg P, Hooper D, Fändriks L, Lonroth H, et al. Substantial production of dopamine in the human gastrointestinal tract. J Clin Endocrinol Metab. 1997 Nov;82(11):3864-3871. DOI: 10.1210/jcem.82.11.4339. PMID:9360553.
23. Volkow ND, Wang GJ, Kollins SH, Wigal TL, Newcorn JH, Telang F, et al. Evaluating dopamine reward pathway in ADHD: Clinical implications. JAMA. 2009;302(10):1084-91. DOI: 10.1001/jama.2009.1308. PMID:19738093.
24. Martínez GÁ, Miguel MDS, Diéguez FJ. New advances in attention-deficit/hyperactivity disorder-like dogs. Animals. 2024;14(14):2067. DOI: 10.3390/ani14142067.
25. Sorathia SJ, Chippa V, Rivas JM. Small intestinal bacterial overgrowth [updated 2023 Apr 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546634/
26. Mahdavi-Roshan M, Salari A, Kheirkhah J, Ghorbani Z. The effects of probiotics on inflammation, endothelial dysfunction, and atherosclerosis progression: A mechanistic overview. Heart Lung Circ. 2022;31(5):e45e71. DOI: 10.1016/j.hlc.2021.09.006.
27. Llorente C, Schnabl B. The gut microbiota and liver disease. Cell Mol Gastroenterol Hepatol. 2015;1(3):275284. DOI: 10.1016/j.jcmgh.2015.04.003. PMID: 26090511; PMCID: PMC4467911.
28. Hrncir T. Gut microbiota dysbiosis: triggers, consequences, diagnostic and therapeutic options. Microorganisms. 2022;10(3):578. DOI: 10.3390/microorganisms10030578. PMID: 35336153; PMCID:PMC8954387.
29. Tyszkowski R, Mehrzad R. Inflammation: A multifaceted and omnipresent phenomenon. In: Mehrzad R, editor. Inflammation and obesity. Cambridge (MA): Academic Press; 2023, p. 19-30. DOI: 10.1016/B978-0-323-909600.00009-6.
30. Silvestrino M, Pirolo M, Bianco A, Castellana S, Sambro DL, Tarallo VD, et al. Idiopathic epilepsy in dogs is associated with dysbiotic faecal microbiota. Anim Microbiome. 2025;7:31. DOI: 10.1186/s42523-02500397-w.
31. Suchodolski JS. Analysis of the gut microbiome in dogs and cats. Vet Clin Pathol. 2022;50 Suppl 1:6-17. DOI: 10.1111/vcp.13031. PMID:34514619; PMCID:PMC9292158.
32. Sung CH, Pilla R, Chen CC, Ishii PE, Toresson L, Jorn AK, et al. Correlation between targeted qPCR assays and untargeted DNA shotgun metagenomic sequencing for assessing the fecal microbiota in dogs. Animals (Basel). 2023;13(16):2597. DOI: 10.3390/ani13162597. PMID: 37627387; PMCID: PMC10451198.
33. Sung CH, Marsilio S, Chow B, Zornow KA, Slovak JE, Pilla R, et al. Dysbiosis index to evaluate the fecal microbiota in healthy cats and cats with chronic enteropathies. J Feline Med Surg. 2022 Jun;24(6):e1-12. DOI: 10.1177/1098612X221077876. EPUB 2022 Mar 10. PMID: 35266809; PMCID: PMC9160961.
34. Al Shawaqfeh MK, Wajid B, Minamoto Y, Markel M, Lidbury JA, et al. A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy. FEMS Microbiol Ecol. 2017 Nov 1;93(11):fix136. DOI: 10.1093/femsec/fix136. PMID: 29040443.
35. O'Neill CA, Monteleone G, McLaughlin JT, Paus R. The gut-skin axis in health and disease: A paradigm with therapeutic implications. Bioessays. 2016 Nov;38(11):1167-76. DOI: 10.1002/bies.201600008. PMID: 27600109.
36. Thomsen M, Künstner A, Wohlers I, Olbrich M, Lenfers T, Osumi T, et al. A comprehensive analysis of gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs. Microbiome. 2023;11:232. DOI: 10.1186/s40168023-01671-2. PMID: 37839933; PMCID: PMC10574387.
37. Minamoto Y, Minamoto T, Isaiah A, Sattasathuchana P, Buono A, Rangachari VR, et al. Fecal short-chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy. J Vet Intern Med. 2019 Jul;33(4):1608-18. DOI: 10.1111/jvim.15513. PMID: 31115173; PMCID: PMC6636987.
38. Banaszak M, Górna I, Woźniak D, Przysławski J, Czyż DS. Association between gut dysbiosis and the occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms. 2023 Feb 24;11(3):573. DOI: 10.3390/microorganisms11030573. PMID: 36985147; PMCID: PMC10052891.
39. Park JS, Guevarra RB, Kim BR, Lee JH, Lee SH, Cho JH, et al. Intestinal microbial dysbiosis in beagles naturally infected with canine parvovirus. J Microbiol Biotechnol. 2019 Sep 28;29(9):1391-400. DOI: 10.4014/jmb.1901.01047. PMID: 31390706.
40. Sung CH, Marsilio S, Chow B, Zornow KA, Slovak JE, Pilla R, et al. Dysbiosis index to evaluate the fecal microbiota in healthy cats and cats with chronic enteropathies. J Feline Med Surg. 2022 Jun;24(6):e1-e12. DOI: 10.1177/1098612X221077876. Epub 2022 Mar 10. PMID: 35266809; PMCID: PMC9160961.
41. Al Shawaqfeh MK, Wajid B, Minamoto Y, Markel M, Lidbury JA, et al. A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy. FEMS Microbiol Ecol. 2017 Nov 1;93(11):fix136. DOI: 10.1093/femsec/fix136. PMID: 29040443.
42. O'Neill CA, Monteleone G, McLaughlin JT, Paus R. The gut-skin axis in health and disease: A paradigm with therapeutic implications. Bioessays. 2016;38(11):116776. DOI: 10.1002/bies.201600008. PMID: 27623616.
43. Thomsen M, Künstner A, Wohlers I, Olbrich M, Lenfers T, Osumi T, et al. A comprehensive analysis of gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs. Microbiome. 2023;11(1):232. DOI: 10.1186/s40168-023-01671-2. PMID: 37917684; PMCID: PMC10613883.
44. Minamoto Y, Minamoto T, Isaiah A, Sattasathuchana P, Buono A, Rangachari VR, et al. Fecal short-chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy. J Vet Intern Med. 2019;33(4):1608-18. DOI: 10.1111/jvim.15518. PMID: 31140678; PMCID: PMC6717704.
45. Banaszak M, Górna I, Woźniak D, Przysławski J, Czyż DS. Association between gut dysbiosis and the occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms. 2023 Feb 24;11(3):573. DOI: 10.3390/microorganisms11030573. PMID: 36985147; PMCID: PMC10052891.
46. Park JS, Guevarra RB, Kim BR, Lee JH, Lee SH, Cho JH, et al. Intestinal microbial dysbiosis in Beagles naturally infected with canine parvovirus. J Microbiol Biotechnol. 2019;29(9):1391-1400. DOI: 10.4014/jmb.1901.01047. PMID: 31378835.
47. Nagahara T, Ohno K, Nakagawa T, Koshino GY, Chambers JK, Uchida K, et al. Analysis of fecal microbial profiles in dogs with intestinal lymphangiectasia. J Vet Med Sci. 2023 Feb 10;85(2):199-206. DOI: 10.1292/jvms.22-0172. Epub 2023 Jan 2. PMID: 36596562; PMCID: PMC10017289.
48. Bourke E, Milne MD, Stokes GS. Caecal pH and ammonia in experimental uraemia. Gut. 1966 Oct;7(5):558-61. DOI: 10.1136/gut.7.5.558. PMID: 5929271; PMCID: PMC1552491.
49. Vaziri ND, Yuan J, Rahimi A, Ni Z, Said H, Subramanian VS. Disintegration of colonic epithelial tight junction in uremia: A likely cause of CKDassociated inflammation. Nephrol Dial Transplant. 2012 Jul;27(7):2686-93. DOI: 10.1093/ndt/gfr624. PMID: 22121298; PMCID: PMC3382203.
50. Summers S, Quimby J. Insights into the gut-kidney axis and implications for chronic kidney disease management in cats and dogs. Vet J. 2024 Aug;306:106181. DOI: 10.1016/j.tvjl.2024.106181. Epub 2024 Jun 17. PMID: 38897377.
51. Kim KR, Kim SM, Kim JH. A pilot study of alterations of the gut microbiome in canine chronic kidney disease. Front Vet Sci. 2023 Aug 24;10:1241215. DOI: 10.3389/fvets.2023.1241215. PMID: 37691637; PMCID: PMC10484476.
52. Isaiah A, Parambeth JC, Steiner JM, Lidbury JA, Suchodolski JS. The fecal microbiome of dogs with exocrine pancreatic insufficiency. Anaerobe. 2017 Apr;45:50-8. DOI: 10.1016/j.anaerobe.2017.02.010. PMID: 28235536.
53. Chandu VV, Naik IH, Kakada D. Canine exocrine pancreatic insufficiency: A review. Sci World. 2024 Oct;4(10):3999-4005. DOI: 10.5281/zenodo.14010826.
54. Li Q, Lebel LÉ, Loughran KA, Huh TP, Suchodolski JS, Oyama MA. Gut dysbiosis and its associations with gut microbiota-derived metabolites in dogs with myxomatous mitral valve disease. M-Systems. 2021 Apr 20;6(2):e00111-21. DOI: 10.1128/mSystems.00111-21. PMID: 33879495; PMCID: PMC8546968.
55. Seo J, Matthewman L, Xia D, Wilshaw J, Chang YM, Connolly DJ. The gut microbiome in dogs with congestive heart failure: A pilot study. Sci Rep. 2020 Aug 13;10:13777. DOI: 10.1038/s41598-020-70826-0.
56. Kummen M, Hov JR. The gut microbial influence on cholestatic liver disease. Liver Int. 2019 Jul;39(7):118696. DOI: 10.1111/liv.14153. EPUB 2019 Jun 17. PMID: 31125502.
57. Habermaass V, Olivero D, Gori E, Mariti C, Longhi E, Marchetti V. Intestinal microbiome in dogs with chronic hepatobiliary disease: Can we talk about the gut-liver axis? Animals (Basel). 2023 Oct 11;13(20):3174. DOI: 10.3390/ani13203174. PMID: 37893898; PMCID: PMC10603696.
58. Slead TS, Callahan BJ, Schreeg ME, Seiler GS, Stowe DM, Peril AMA, et al. Microbiome analysis of bile from apparently healthy cats and cats with suspected hepatobiliary disease. J Vet Intern Med. 2023 Nov;37(6):2178-87. DOI: 10.1111/jvim.16852.
59. Dell'Anno F, Guardone L, Listorti V, Razzuoli E. Microbiome in cancer: A comparative analysis between humans and dogs. Vet J. 2024 May;305:106145. DOI: 10.1016/j.tvjl.2024.106145.
60. Breczko WJ, Bubak J, Miszczak M. The importance of intestinal microbiota and dysbiosis in the context of the development of intestinal lymphoma in dogs and cats. Cancers (Basel). 2024 Jun 18;16(12):2255. DOI: 10.3390/cancers16122255. PMID: 38927960; PMCID: PMC11202240.