Scientists discuss the need to rethink microbiome biomarkers in the context of microbial ecology

Gut microbiota has been related to several pathologies over the past two decades. Nevertheless, not all pathology-associated microbiome signatures have been found to be equally consistent and the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated.

A new comment published in Nature Microbiology, led by Dr. Jeroen Raes from the VIB Centre for the Biology of Disease/Vrije Universiteit Brussel (VUB)/KU Leuven-University of Leuven (Belgium), explores the role of microbial ecology in distinguishing relevant clinical features in microbiome studies.

Microbiota richness, defined as the number of species in a biological community—not taking into account each one’s abundance—has usually been considered a hallmark of gut health and stability. Meanwhile, the diversity of a bacterial sample measures how statistically difficult it would be to predict the identity of the next bacterial individual sampled, taking into account what is already known about the community. Although all healthy microbiomes are similar, each incident of dysbiosis is slightly different and identifying a highly sensitive and specific gut microbial biomarker of disease is difficult. In other words, the Ana Karenina principle applies, where “All happy families are alike; each unhappy family is unhappy in its own way.”

First, the authors explain that although increased microbiome richness and diversity have been considered hallmarks of a healthy gut ecosystem and associated with microbiota stability and resilience to perturbation, recent broad population-wide cohort studies have identified multiple confounder factors that may explain microbiota variation. These factors include transit time and stool consistency, age, dietary habits and medication, and they may all explain an important part of inter- and intra-individual variation in community composition and richness, regardless of host health (these covariates may even improve the identification and reproducibility of microbial biomarkers).

According to the researchers, “stool microbiota composition and metabolism should be considered as if they represented snapshots of an ecosystem caught in a process of dynamic development.” Indeed, gut microbial succession events seem to be influenced by a constant variation occurring over time and among individuals due to host physiology- and lifestyle-selective pressure, rather than following deterministic patterns. For instance, while microbial population density and richness increase with transit time, water is reabsorbed and affects lumen content. Furthermore, increased quantitative or relative microbiome profiles in parallel with longer transit times lead to a shift in microbial metabolic activity, which is enriched with taxa with a more pronounced proteolytic metabolic profile.

Taking into account the context of gut ecology, fecal microbiota richness could reflect a temporal stage of ecosystem development through the gut and as an isolated biomarker does not provide information related to gut microbiota stability, resilience and host health. Thus, increased richness and diversity should not be systematically considered as a desirable endpoint in nutrition studies that target the gut microbiome. Alternatively, focusing on gut microbiota’s metabolic activity might be a more reasonable read-out of intervention success than microbiota richness or diversity.

On the whole, the ecological succession-based interpretation of microbiota variation may lead to redefining the fecal microbiota beyond a sample of a homogenous and stable gut microbiota in the clinical setting. All together, these data highlight the need to rethink microbiome biomarkers in the context of gut ecology. These results also provide insights into the importance of a functional and ecological assessment of gut microbiome variation in clinical studies.

 

Reference:

Falony G, Vieira-Silva S, Raes J. Richness and ecosystem development across faecal snapshots of the gut microbiota. Nat Microbiol. 2018; 3(5):526-8. doi: 10.1038/s41564-018-0143-5.

GMFH Editing Team
GMFH Editing Team