Microbiome in Complex Disease

An imbalance between microorganisms in human microbiome is responsible for many complex diseases. The relationship is complex. In a new review article published in the International Journal of Molecular Sciences, researchers analyzed over 24,000 scientific papers on gut microbiome in metabolic (n=6109 papers), immune (n=7434), autoimmune (n=1927), cardiovascular (n=2605), brain diseases (n=4216) and various cancers (n=5564).  Most papers were written about the role of microbiome in obesity (n=5342), while the smallest subset was about heart failure (n=261). 

Complex diseases occur due to interaction of genetic and environmental factors.

Gut microbes and their metabolites play important roles as environmental factors. The metabolites - such as short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic microbes in the gut, can protect us from pathogen invasion by activating immune defense. Lactobacillus rhamnose, for example, strengthens the ability of the T cell response. Lactobacillus sakei reduces the level of serum IgE and IL4. Acinetobacter iwoffii improves respiratory hyperresponsiveness by blocking the recruitment of dendritic cells in the lungs. Lactobacillus casei ATCC334 can produce iron pigment, which plays a role in inhibiting tumor progression. Some microorganisms may be also used in the treatment of hypertension, cardiovascular and other diseases. 

Bacterial biofilms (bacterial colonies self-organized in complex structures), on the other hand, can interrupt human immune system in many harmful ways. Bacteroides fragilis biofilms are implicated in destruction of mucosal epithelium, thus promoting migration of harmful species and helping them escape body's defense mechanisms. Small metabolites such as trimethylamine oxide (TMAO) produced by some gut bacteria could induce cardiac hypertrophy and fibrosis. 

Some proteases secreted by microbes are contributing to developing diseases, such as arterial sclerosis, skin disease, enteritis and cardiovascular disease and others. M. globosa (a common skin color fungi), on the other hand, secretes proteinase MgSAP1 that rapidly hydrolyses Staphylococcus protein A (SpA) and prevents S. aureus biofilm formation, helping to maintain a healthy skin. Bacteria can also secrete amino acid-derived antibiotics to fight diseases - e.g., Clostridium scindens and C. sordellii that help to inhibit the growth of C. difficile. 

The new review discusses these and many other mechanisms in complex disease as well as potential cures and dietary interventions.

REFERENCES

Yu D, Meng X, de Vos WM, Wu H, Fang X, Maiti AK. Implications of Gut Microbiota in Complex Human Diseases. International Journal of Molecular Sciences. 2021, 22(23):12661.