Changes

A balanced gut microbiota heavily contributes to the normal physiological functioning of the host through protection against potential pathogens, encouraging immune system tolerance and normal metabolism.<ref name=":1">Pilla R & Suchodolski JS. The role of the canine microbiome and metabolome in health and gastrointestinal disease, ''Frontiers in Veterinary Science'' 2020; 6</ref> Dysbiosis can simply be defined as qualitative and quantitative changes to the composition of the microbiota when compared to a group of healthy individuals. This state of dysbiosis can be harmful to the host through alterations in bacterial metabolism and the overgrowth of potentially pathogenic microorganisms. It is thought that the growth of these bacteria in the gastrointestinal tract results in the release of possible toxins that play a role in many chronic diseases.<ref name=":2">Hawrelak JA & Myers SP. The causes of intestinal dysbiosis: a review, ''Alternative Medicine Review'' 2004; 9(2):180-197</ref>

A balanced gut microbiota heavily contributes to the normal physiological functioning of the host through protection against potential pathogens, encouraging immune system tolerance and normal metabolism.<ref name=":1">Pilla R & Suchodolski JS. The role of the canine microbiome and metabolome in health and gastrointestinal disease, ''Frontiers in Veterinary Science'' 2020; 6</ref> Dysbiosis can simply be defined as qualitative and quantitative changes to the composition of the microbiota when compared to a group of healthy individuals. This state of dysbiosis can be harmful to the host through alterations in bacterial metabolism and the overgrowth of potentially pathogenic microorganisms. It is thought that the growth of these bacteria in the gastrointestinal tract results in the release of possible toxins that play a role in many chronic diseases.<ref name=":2">Hawrelak JA & Myers SP. The causes of intestinal dysbiosis: a review, ''Alternative Medicine Review'' 2004; 9(2):180-197</ref>

Studies have demonstrated that diet, lifestyle, stress and antibiotics amongst many other factors can contribute to dysbiosis. The main symptoms often associated with dysbiosis are diarrhoea, vomiting, depression, weight loss and lethargy. However, dysbiosis has been linked to more serious long-term diseases, not only confined to the gut, but also those affecting other body systems.

Studies have demonstrated that diet, lifestyle, stress and antibiotics amongst many other factors can contribute to dysbiosis. The main symptoms often associated with dysbiosis are diarrhoea, vomiting, depression, weight loss and lethargy. However, dysbiosis has been linked to more serious long-term diseases, not only confined to the gut, but also those affecting other body systems.

Gut dysbiosis can be measured and quantified through a PCR-based algorithm called the “Dysbiosis Index”. This mathematical model uses the quantification of total bacteria and a panel of several common bacterial groups to calculate the Dysbiosis Index (DI). Negative DI values indicate normobiosis, and positive DI values indicate dysbiosis. The DI allows us to monitor changes to dysbiosis over the course of a disease or in response to treatments. <ref name=":1"/>Studies have demonstrated that DI is increased in dogs with chronic enteropathies.<ref name=":3">Minamoto Y, Minamoto T, Isaiah A, et al. Fecal short-chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy, ''Journal of Veterinary Internal Medicine'' 2019; 33:1608-1618</ref>,<ref name=":4">Giaretta PR, Rech RR, Guard BC, et al. Comparison of intestinal expression of the apical sodium-dependent bile acid transporter between dogs with and without chronic inflammatory enteropathy, ''Journal of Veterinary Internal Medicine'' 2018; 32:1918-1926</ref>,<ref name=":5">Guard BC, Honneffer JB, Jergens AE, et al. Longitudinal assessment of microbial dysbiosis, fecal unconjugated bile acid concentrations, and disease activity in dogs with steroid-responsive chronic inflammatory enteropathy, ''Journal of Veterinary Internal Medicine'' 2019; 33:1295-1305</ref>

Gut dysbiosis can be measured and quantified through a PCR-based algorithm called the “Dysbiosis Index”. This mathematical model uses the quantification of total bacteria and a panel of several common bacterial groups to calculate the Dysbiosis Index (DI). Negative DI values indicate normobiosis, and positive DI values indicate dysbiosis. The DI allows us to monitor changes to dysbiosis over the course of a disease or in response to treatments. <ref name=":1"/>Studies have demonstrated that DI is increased in dogs with chronic enteropathies.<ref name=":3">Minamoto Y, Minamoto T, Isaiah A, et al. Fecal short-chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy, ''Journal of Veterinary Internal Medicine'' 2019; 33:1608-1618</ref>,<ref name=":4">Giaretta PR, Rech RR, Guard BC, et al. Comparison of intestinal expression of the apical sodium-dependent bile acid transporter between dogs with and without chronic inflammatory enteropathy, ''Journal of Veterinary Internal Medicine'' 2018; 32:1918-1926</ref>,<ref name=":5">Guard BC, Honneffer JB, Jergens AE, et al. Longitudinal assessment of microbial dysbiosis, fecal unconjugated bile acid concentrations, and disease activity in dogs with steroid-responsive chronic inflammatory enteropathy, ''Journal of Veterinary Internal Medicine'' 2019; 33:1295-1305</ref>

Dogs with acute diarrhoea and chronic enteropathies such as inflammatory bowel disease (IBD) and haemorrhagic gastroenteritis (HGE) are shown to have a strong dysbiosis with a decrease in short-chain fatty acid producing bacteria, increase in Clostridium genus bacteria and significant decrease in microbial diversity compared to healthy dogs.<ref name=":6">Suchodolski JS, Markel ME, Garcia-Mazcorro JF et al. The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease, ''PLOS ONE'' 2012; 7(12):e51907</ref>,<ref name=":7">Unterer S, Busch K, Leipig M, Hermanns W, Wolf G, Straubinger R, Mueller R, Hartmann K. Endoscopically Visualized Lesions, Histologic Findings, and Bacterial Invasion in the Gastrointestinal Mucosa of Dogs with Acute Hemorrhagic Diarrhea Syndrome, ''Journal of Veterinary Internal Medicine'' 2014; 28:52-58</ref> Similarly, it has  been demonstrated that cats with diarrhoea and chronic enteropathies have significant dysbiosis. <ref name=":8">Suchodolski JS, Foster ML, Sohail MU et al. The fecal microbiome in cats with diarrhea, ''PLOS ONE'' 2015; 10:e0127378</ref>,<ref name=":9">Bierlein M, Hedgespeth BA, Azcarate-Peril MA, Stauffer SH, Gookin JL. Dysbiosis of fecal microbiota in cats with naturally occurring and experimentally induced Tritrichomonas foetus infection, ''PLOS ONE'' 2021; 16(2):e0246957</ref> Whether these changes play a causal role in disease development or occur as an effect of gastrointestinal pathology still requires further research.

Dogs with acute diarrhoea and chronic enteropathies such as inflammatory bowel disease (IBD) and haemorrhagic gastroenteritis (HGE) are shown to have a strong dysbiosis with a decrease in short-chain fatty acid producing bacteria, increase in Clostridium genus bacteria and significant decrease in microbial diversity compared to healthy dogs.<ref name=":6">Suchodolski JS, Markel ME, Garcia-Mazcorro JF et al. The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease, ''PLOS ONE'' 2012; 7(12):e51907</ref>,<ref name=":7">Unterer S, Busch K, Leipig M, Hermanns W, Wolf G, Straubinger R, Mueller R, Hartmann K. Endoscopically Visualized Lesions, Histologic Findings, and Bacterial Invasion in the Gastrointestinal Mucosa of Dogs with Acute Hemorrhagic Diarrhea Syndrome, ''Journal of Veterinary Internal Medicine'' 2014; 28:52-58</ref> Similarly, it has  been demonstrated that cats with diarrhoea and chronic enteropathies have significant dysbiosis. <ref name=":8">Suchodolski JS, Foster ML, Sohail MU et al. The fecal microbiome in cats with diarrhea, ''PLOS ONE'' 2015; 10:e0127378</ref>,<ref name=":9">Bierlein M, Hedgespeth BA, Azcarate-Peril MA, Stauffer SH, Gookin JL. Dysbiosis of fecal microbiota in cats with naturally occurring and experimentally induced Tritrichomonas foetus infection, ''PLOS ONE'' 2021; 16(2):e0246957</ref> Whether these changes play a causal role in disease development or occur as an effect of gastrointestinal pathology still requires further research.

Interestingly, dysbiosis has been linked to many non-gastrointestinal diseases in humans and also in dogs. In humans, dysbiosis is associated with type 1 and type 2 diabetes,<ref name=":10">Rosa F, Sofia DV, Sara N, Flávio R. Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy, ''BBA Molecular Basis of Disease'' 2019; 1865(7):1876-1897</ref>,<ref name=":11">Gülden E, Wong S, Wen L. The gut microbiota and Type1 Diabetes, Clinical Immunology 2015; 159(2):143-153</ref> Parkinsons disease,<ref name=":12">Daniele P, Rocco C, Valeria U, Alessio F, Mariangela P, Nicola BM, Silvia B, Alessandro S, Alessandro D. Dysbiosis of gut microbiota in a selected population of Parkinson's patients, ''Parkinsonism & Related Disorders'' 2019; 65:124-130</ref>,<ref name=":13">José FBC & Marlene AJ. The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease, ''Neuroscience'' 2020; 432:160-173</ref> mental health including depression, <ref name=":14">Capuco A, Urits I, Hasoon J, et al. Gut Microbiome Dysbiosis and Depression: a Comprehensive Review, ''Current Pain and Headache Report''s 2020; 24(36)</ref>,<ref name=":15">Danielle M, Adriano JMCF, Caren NSdS, João Q, Tatiana B, Hélio VNJ, David FdL. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness, ;;Journal of Affective Disorders;; 2017; 208:22-32</ref>,<ref name=":16">Capuco A, Urits I, Hasoon J, et al. Current Perspectives on Gut Microbiome Dysbiosis and Depression, ''Advances in Therapy'' 2020; 37:1328-1346</ref> colorectal cancer,<ref name=":17">Gao R, Gao Z, Huang L, Qin H. Gut microbiota and colorectal cancer. ''European Journal of Clinical Microbiology & Infectious Diseases'' 2017 ; 36(5): 757-769</ref> obesity, <ref name=":18">Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. ''Proceedings of the National Academy of Sciences of the United States of America'' 2005; 102(31):11070-11075</ref> and many other diseases. In dogs, meningoencephalomyelitis of unknown origin (MUO) is linked with dysbiosis. More specifically, there is strong evidence that a high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease.<ref name=":19">Jeffery ND, Barker AK, Alcott CJ et al. The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs. ''PLOS One'' 2017; 12(1):e0170589</ref> Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease19. Additionally, dogs with congestive heart failure are shown to have an increased abundance of Proteobacteria due to an increase in Enterobacteriaceae and Escherichia coli.<ref name=":20">Seo J, Matthewman L, Xia D, et al. The gut microbiome in dogs with congestive heart failure: a pilot study, ''Scientific Reports'' 2020; 10(13777)</ref> Thus concluding dogs with congestive heart failure are likely to have dysbiosis, with further studies in humans also suggesting this.

Interestingly, dysbiosis has been linked to many non-gastrointestinal diseases in humans and also in dogs. In humans, dysbiosis is associated with type 1 and type 2 diabetes,<ref name=":10">Rosa F, Sofia DV, Sara N, Flávio R. Diabetic gut microbiota dysbiosis as an inflammaging and immunosenescence condition that fosters progression of retinopathy and nephropathy, ''BBA Molecular Basis of Disease'' 2019; 1865(7):1876-1897</ref>,<ref name=":11">Gülden E, Wong S, Wen L. The gut microbiota and Type1 Diabetes, Clinical Immunology 2015; 159(2):143-153</ref> Parkinsons disease,<ref name=":12">Daniele P, Rocco C, Valeria U, Alessio F, Mariangela P, Nicola BM, Silvia B, Alessandro S, Alessandro D. Dysbiosis of gut microbiota in a selected population of Parkinson's patients, ''Parkinsonism & Related Disorders'' 2019; 65:124-130</ref>,<ref name=":13">José FBC & Marlene AJ. The Link between Gut Dysbiosis and Neuroinflammation in Parkinson’s Disease, ''Neuroscience'' 2020; 432:160-173</ref> mental health including depression, <ref name=":14">Capuco A, Urits I, Hasoon J, et al. Gut Microbiome Dysbiosis and Depression: a Comprehensive Review, ''Current Pain and Headache Report''s 2020; 24(36)</ref>,<ref name=":15">Danielle M, Adriano JMCF, Caren NSdS, João Q, Tatiana B, Hélio VNJ, David FdL. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness, ;;Journal of Affective Disorders;; 2017; 208:22-32</ref>,<ref name=":16">Capuco A, Urits I, Hasoon J, et al. Current Perspectives on Gut Microbiome Dysbiosis and Depression, ''Advances in Therapy'' 2020; 37:1328-1346</ref> colorectal cancer,<ref name=":17">Gao R, Gao Z, Huang L, Qin H. Gut microbiota and colorectal cancer. ''European Journal of Clinical Microbiology & Infectious Diseases'' 2017 ; 36(5): 757-769</ref> obesity, <ref name=":18">Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. ''Proceedings of the National Academy of Sciences of the United States of America'' 2005; 102(31):11070-11075</ref> and many other diseases. In dogs, meningoencephalomyelitis of unknown origin (MUO) is linked with dysbiosis. More specifically, there is strong evidence that a high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease.<ref name=":19">Jeffery ND, Barker AK, Alcott CJ et al. The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs. ''PLOS One'' 2017; 12(1):e0170589</ref> Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease19. Additionally, dogs with congestive heart failure are shown to have an increased abundance of Proteobacteria due to an increase in Enterobacteriaceae and Escherichia coli.<ref name=":20">Seo J, Matthewman L, Xia D, et al. The gut microbiome in dogs with congestive heart failure: a pilot study, ''Scientific Reports'' 2020; 10(13777)</ref> Thus concluding dogs with congestive heart failure are likely to have dysbiosis, with further studies in humans also suggesting this.