The UEG week on its 2019 edition brought interesting findings on how the gut microbiota health is related to the prevention, development and cure of major diseases.
Development and variations of the healthy gut microbiota
The microbiota is a complex microbial community established in individually variant ecosystems (as the human gut). For that reason, its shaping depends of a wide range of influences and insults as presented by Georgina Hold (University of South Wales, Australia). Trillions of microbes have co-evolved with humans, and are in a continuous adaptation towards the human physiology. Since birth, such variations depend of factors like delivery mode, diet, geography, early exposures (pollution and antibiotics), ageing and host genetics. However, environmental factors seem to play a more important role in microbiota modelling than host genetics . Early life microbiota is an important determinant to understand chronic diseases development, particularly in urban societies, for example asthma, allergies, eczema, inflammatory bowel disease (IBD), coeliac disease, obesity.
There is not ‘one’ normal microbiota pattern in healthy individuals, since in the microbiota metabolic and functional patterns are not species driven. Likewise, in the gut microbiota shaping, inter-country variants are more important than inter-individual variants . Self-reported results from the HELIUS cohort by Stijn Meijnikman (Academic Medical Centre, Netherlands) showed that bacterial diversity is related to ethnic background (probably driven by diet and ancestries). It is considered that a high-Bacteroides/low-Prevotella ratio is related with a westernized diet; however, microbiota functionality analysis usually shows contradictory results. As a consequence ‘dysbiosis’ is an imprecise term if “healthy”, “unhealthy” or just “different” microbiota are not defined on each case.
Microbiota and intestinal disease
The interaction between the microbiota and the host is a 2-way communication, Lipopolysaccharide (LPS) is an important mediator produced by Gram-negatives that triggers intestinal inflammation, besides adipose cell-proliferation and insulin resistance as explained by Remy Burcelin (Paul-Sabatier University, France). Bacterial translocation to the adipose tissue is also an important feature in metabolic syndrome. Furthermore, high concentrations of bacterial DNA on adipocytes can be considered as molecular biomarkers of type 2 diabetes.
Irritable bowel syndrome (IBS) is a complex disease where the microbiota and the host interplay in its physiopathology as presented by Magnus Simrén (Sahlgrenska University Hospital, Sweden). There are IBS patients where there is not a clear microbiota signature when comparing with healthy controls. However, some specific patterns have been associated with symptoms severity . By modulating the microbiota patterns on IBS patients (by probiotics or non-absorbable antibiotics) symptoms can be improved.
Effect of drugs intake on the gut microbiota
Drugs intake interacts directly with the gut microbiota as explained by Rinse K. Weersma (University Medical Center Groningen, Netherlands). There are three scenarios: the drug affects the gut microbiota changing its composition/function, the microbiota metabolizes the drug making it to activate/inactivate, or the microbiota has indirect effects on the drug response . In the first case, the use of proton pump inhibitors has shown the increase of potentially harmful bacteria (Enterococcus, Streptococcus, Staphylococcus and Escherichia). Other drugs have reported to have a significant impact in the gut microbiota like metformin, laxatives, antidepressants and antibiotics. In the second scenario the most commonly studied drugs are sulfasalazine (which is activated by the microbiota), and digoxin (which is inactivated by specific bacterial strains).
The indirect effect of the gut microbiota on the drug response has been reported in antitumoral immunotherapies as presented by Harry Sokol (Saint-Antoine Hospital, France). The use of anti PD-1 immunotherapy on melanoma, non-small cell lung cancer, renal carcinoma and others is directly affected by the use of antibiotics. Additionally, the positive effect of ipilimumab on melanoma is directly related with the presence of Faecalibacterium prausnitzii .
Other studies have reported similar results but with different bacteria like Akkermansia muciniphila, however the mechanisms seem that these bacteria have an important anti-inflammatory effect via CTL4 pathway.