Richness of human gut microbiome correlates with metabolic markers

Abstract

We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities

Subspecies in the global human gut microbiome

“…This association is independent of the specific abundance of the subspecies in the individuals. Furthermore, individuals harboring subspecies MGSS2 and MGSS3 appeared to have lower community diversity (Fig 3D; Shannon diversity index), in line with previous observations of a negative correlation between community diversity and host BMI (Le Chatelier et al , 2013). …”

“…The TLR5 receptor in human epithelial cells (colonocytes) recognizes the flagellum and induces a downstream cascade which results in initiation of pro‐inflammatory pathways and secretion of IL‐8 (Neville et al , 2013). Such low‐grade inflammation has been repeatedly linked to obesity, increased insulin resistance, and diabetes (Gregor & Hotamisligil, 2011) providing a potential explanation for our observation that BMI and insulin resistance are significantly higher in individuals who predominantly harbor the flagellum‐carrying subspecies (MGSS2 and MGSS3) in the Danish (Le Chatelier et al , 2013) and Swedish (Karlsson et al , 2013) cohorts (Fig 3D). This association is independent of the specific abundance of the subspecies in the individuals.…”

“…At least nine genes related to bacterial chemotaxis and flagellar assembly are specific to E. eligens MGSS3. Only 7 and 10% of samples from the Danish (Le Chatelier et al , 2013) and the Swedish study contain this subspecies (14 and 4 samples, respectively, however not statistically significant due to small sample size). Such striking functional differences between subspecies and their associations with host phenotypes have implication for disease treatment, which could, for example, aim at replacing the “detrimental” subspecies by one without the respective trait.…”

“…In addition to these global associations, separate statistical tests within each study cohort revealed a strong negative association between type 2 diabetes status specifically in Chinese individuals (Qin et al , 2012) and Bacteroides coprocola MGSS3 , which is enriched in healthy individuals (Fisher test P ‐value 2.98e‐05). This association was, however, not significant in the two type 2 diabetes case–control studies with smaller cohorts (Karlsson et al , 2013; Le Chatelier et al , 2013). …”

“…To this end, we assessed the microbial genetic landscape of 2,144 deeply sequenced human stool metagenomes from nine countries, spanning three continents, including published (Huttenhower et al , 2012; Qin et al , 2012; Karlsson et al , 2013; Le Chatelier et al , 2013; Zeller et al , 2014) as well as 298 newly generated ones (Table EV1). The newly sequenced samples include a Kazakh cohort as well as three individuals from Germany that have been sampled over an extended period of time (see Materials and Methods).…”