Why studying the gut microbes could help to cure?

Exploring the gut-organ axis in human health and disease 

November, 2022 l Sylvie Maubant, Ph.D. 

The human intestine hosts diverse microbial communities, with bacteria as the most numerous members, that play a significant role in maintaining health and homeostasis throughout the body.  But how do gut microbes talk to different organs?  

Microbial metabolites have been identified as key mediators for the communication via multiple routes including neural, metabolic, endocrine and immune pathways. The complex interactions between the gut microbiota and the different organs result in the formation of the gut-organ axis. Within these axes, any changes in intestinal microbiota composition may not only have an impact locally on the gut, but also influence other distant organs and so be associated with various diseases.  Here, we explore five of those axes. 

• Gut-brain axis 

Evidence is accumulating that the gut-brain axis has an important role in risk and progression of many malignancies such as Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis, autism spectrum disorder, depression, anxiety, stress and schizophrenia. This is supported by several works from human studies and animal models used to decipher mechanisms of action highlighting a change in gut microbiota composition in a pathological situation versus control condition. Indeed, an increased abundance of Helicobacter pylori and Escherichia coli, for example, was shown to induce the progression of several neurological disorders and symptoms including the alpha-synuclein aggregation and decreased motor performance (hallmarks of PD), hyperphosphorylation of tau protein and amyloid-beta load (biomarkers of AD)¹. In addition, alterations in levels of potentially beneficial gut metabolites (e.g. short chain fatty acids, SCFAs) could also have a role in disorders of the gut-brain axis².  

• Gut-kidney axis 

Acute kidney injury, chronic kidney disease, Immunoglobulin A nephropathy and nephrolithiasis are among the kidney diseases associated with gut dysbiosis but without showing any apparent pattern. According to recent studies, microbial alterations may trigger production of harmful metabolites such as uremic toxins and trimethylamine and a decrease in beneficial ones such as SCFAs in patients with a renal pathology³.  

• Gut-liver axis 

Shifts in gut microbiota composition have been observed consistently in individuals with various liver diseases and along different stages of their development: alcohol-related liver disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. For example, several works have found differences in the gut microbiota of patients with NAFLD compared to healthy controls (e.g. increased abundance of Proteobacteria and Firmicutes as well as a decrease in Bacteroidetes and Prevotellaceae)⁴. An increasing body of evidence showed that trimethylamine-N-oxide was correlated with NAFLD underlying its negative role while SCFAs levels were reduced in this context⁵.  

• Gut-lung axis 

Some studies have reported a gut dysbiosis in several lung pathologies including asthma, chronic obstructive pulmonary disease, cystic fibrosis and lung cancer along with Covid-19. As an illustration, the levels of Akkermansia muciniphila and Faecalibacterium prausnitzii were found to be reduced in the gut microbiota of children with allergic asthma⁶. To be noted that lung diseases have been also associated with perturbations of the lung microbiota thus adding here another level of crosstalk between gut and lungs. Supplementary data have emphasized that individuals with lower levels of SCFAs were more susceptible to lung infections⁷.  

• Gut-skin axis 

The microbiota plays an important role in a wide variety of skin disorders such as psoriasis, atopic dermatitis (AD) and acne. As expected, the skin microbiota is altered in this context, but surprisingly many skin diseases are accompanied also by an imbalance in gut microbiota (e.g. a lower abundance of Firmicutes and increased levels of Bacteroides in acne patients; an enrichment in Faecalibacterium prausnitzii, Clostridium and Escherichia and lower levels of Akkermansia, Bacteroidetes and Bifidobacterium in AD individuals) and production of metabolites (e.g. decreased levels of butyrate and propionate i.e. SCFAs in AD patients)⁸.  

A dysbiosis in gut microbiota has been associated with several diseases targeting distant organs

Even though we are still facing the chicken or egg dilemma in much cases, it is clear that the intestinal microbiota is now recognized as the cornerstone in the host physiopathology. This field has received an increasing attention over the last decade helping to partially untangle the intricate networks of gut-organ axis. While there is no consensus yet about gut microbiome-derived signature in a pathological context, these major advances should encourage the development of new diagnostic approaches and innovative personalized therapies.  

For instance, Akkermansia muciniphila is considered to be a promising candidate, a history that has started in 2004⁹. The lack or decreased abundance of this gut commensal bacterium has been associated with multiple diseases in both mouse models and humans which prompted further investigations. Beneficial effects of Akkermansia muciniphila have been notably demonstrated in cancer with an improvement of the response to immunotherapies such as PD-1 blockade. The road to success is often long but it offers new hopes for patients.  

About the author 

This blog post was written by Sylvie Maubant, Ph.D., a Biology Scientist at Oncodesign Services. In her current role, Sylvie is involved in microbiome R&D programs for customers in various areas (oncology, immuno-oncology, inflammatory diseases, infectious diseases, dermocosmetics and nutrition). 

If you would like to know more about microbiome studies and how Oncodesign Services can help your projects, contact our team via the contact form here. 

KNOW MORE ABOUT MICROBIOME

References : 

1. Liu et al (2022). Microbiota and the gut-brain-axis: implications for new therapeutic design in the CNS. EBioMedicine, 77: 103908.
2. O’Riordan et al (2022). Short chain fatty acids: microbial metabolites for gut-brain axis signaling. Mol Cell Endocrinol, 546: 111572. 
3. Stavropoulou et al (2021). Focus on the gut-kidney axis in health and disease. Front Med, 7: 620102.
4. Forlano et al (2022). Gut microbiota – A future therapeutic target for people with non-alcoholic fatty liver disease: a systematic review. Int J Mol Sci, 23 (15): 8307. 
5. Dai et al (2020). Microbial metabolites: critical regulators in NAFLD. Front Microbiol, 11: 567654. 
6. Demirci et al (2019). Reduced Akkermansia muciniphila and Faecalibacterium prausnitzii levels in the gut microbiota of children with allergic asthma. Allergol Immunopathol, 47 (4): 365.
7. Machado et al (2021). Short-chain fatty acids as a potential treatment for infections: a closer look at the lungs. Infect Immun, 89 (9): e0018821. 
8. De Pessemier et al (2021). Gut-skin axis: current knowledge of the interrelationship between microbial dysbiosis and skin conditions. Microorganisms, 9 (2): 353. 
9. Cani et al (2022). Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol, 19: 625.