Research Article: Gut Microbiota Signatures Predict Host and Microbiota Responses to Dietary Interventions in Obese Individuals

Date Published: March 6, 2014

Publisher: Public Library of Science

Author(s): Katri Korpela, Harry J. Flint, Alexandra M. Johnstone, Jenni Lappi, Kaisa Poutanen, Evelyne Dewulf, Nathalie Delzenne, Willem M. de Vos, Anne Salonen, Stefan Bereswill.


Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gut microbiota may depend on its composition, and associate with metabolic changes in the host.

Our study involved three independent cohorts of obese adults (n = 78) from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set – test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters.

Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC  =  0.77–1; predicted vs. observed correlation  =  0.67–0.88). Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health.

This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the potential of microbiota signatures for personalized nutrition.

Partial Text

The gut microbiota is an important contributor to human health, and is emerging as a promising target for therapeutic modulation [1], [2]. Obesity-related diseases offer a prime example where intestinal bacteria have recently been implicated as one etiological factor [3]–[5]; hence modifying the gut microbiota represents a potential strategy for successful treatment [3], [6], [7]. However, it is currently impossible to make practical guidelines as to how the microbiota should be modified. Although recent research has identified compositional and functional properties that characterize the intestinal microbiota in healthy individuals [8], we are lacking a definition for a healthy microbiota, mainly because of the vast inter-individual variation [9]. Furthermore, individuals’ responses to dietary interventions are highly variable and poorly predictable – both in terms of host metabolism as well as the gut microbiota – and sometimes even contrary to what was expected from in vitro studies [10]–[13]. Hence, the key challenge for the therapeutic modulation of the gut microbiota is to identify individuals who will benefit from a given intervention, with respect to their microbiota composition, and most importantly, with regard to clinical health markers. Personalized nutritional and pharmaceutical therapy, based on information of the individual’s gut microbiota, have great prospects in the treatment of obesity and related conditions [10], [14].

To study the possibility to differentiate and predict highly individual dietary responses based on the intestinal microbiota, we searched for associations between its baseline composition and the degree of responsiveness of the microbiota, and of the host, to dietary interventions.