As these GEITP pages keep reiterating, virtually any phenotype (trait) reflects the contribution of genetics, epigenetic effects, environmental factors, endogenous influences, and each individual’s microbiome. The topic (phenotype) being discussed herein is obesity, and the contribution of the gut microbiome is being examined.
Indications that changes in the fecal microbiome are linked to development of obesity have resulted in intense research efforts — since the early days of metagenomics. However, understanding an “obesity-associated microbiota constellation” has proved to be challenging. Obesity and obesity-related co-morbidities have clearly been associated with alterations in gut microbiota (including lowered fecal-community richness and decreased abundance of butyrate-producing bacteria). “Microbiome community-typing” analyses have recently identified the Bacteroides2 (Bact2) type of “intestinal microbiota configuration” (i.e. enterotype) — that is associated with systemic inflammation, leading to loose stools in many humans. The Bact2 enterotype is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium, and low microbial cell densities; prevalence of the Bact2 enterotype varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease (IBD).
Reported changes in stool consistency and inflammation status during progression towards obesity and metabolic co-morbidities led authors [see attached article & editorial] to propose that these developments might similarly be correlated with increased prevalence of the potentially dysbiotic (pathological) Bact2 enterotype. By exploring obesity-associated
microbiota alterations in quantitative fecal metagenomes of the MetaCardis Body Mass Index Spectrum cohort (n = 888), authors identified statin therapy as a key co-variate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, authors found that prevalence of the Bact2 enterotype was correlated with body mass index (BMI) — increasing from 3.9% in lean participants to 17.73% in seriously obese participants.
Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted — on the basis of their obesity status — indicating an association of the Bact2 enterotype with a dysbiotic microbiome constellation. Authors also discovered that obesity-associated microbiota dysbiosis is negatively associated with statin treatment (resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants). This was validated in both the accompanying MetaCardis cardiovascular disease datase (n = 282) and an independent Flemish Gut Flora Project population cohort (n = 2,345). Potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population; also, a prospective clinical trial will be needed before considering the application of statins as “microbiota-modulating therapeutics”. 😊
Nature 21 May 2020; 581: 310-315 + editorial pp 263-264