A Microbiome Restoration Strategy Modulates the Gut Microbiome and Metabolic Markers in Healthy Adults

The dramatic increase of chronic diseases in industrialized societies might be driven in part by a disruption of gut microbiome composition and function (e.g., reduced fiber fermentation) and impaired intestinal barrier integrity. We developed a microbiome restoration strategy based on a diet that resembles key aspects of a non-industrialized diet (Non-Ind) and a probiotic Limosilactobacillus reuteri (a species rarely found in microbiome from industrialized populations). Using a randomized controlled pilot study, 30 participants consumed either the Non-Ind diet or their usual diet in a crossover fashion for three weeks each. Participants were also divided into three groups and consumed either a single dose of one of two Lm. reuteri strains or a placebo on day four of each diet period. The Non-Ind diet enhanced the temporal persistence of one of the Lm. reuteri strains, but had no measurable effects on microbiome and host. In contrast, the Non-Ind diet shifted overall fecal microbiome composition (R2=0.015, p=0.001; ADONIS), and significantly altered 56% of Amplicon Sequence Variants obtained from 16S dataset (FDR lower than 0.05), 22% of species-level genome bins, and 21% of metabolic pathways obtained from metagenomic dataset (FDR lower than 0.05). Bacteria fermentation was enhanced, exhibited by increased concentration of total fecal short-chain fatty acids (+10.7%, p=0.03) and reduced fecal pH (-3.8%, p=0.002). Furthermore, we observed reductions in six chronic disease risk markers (all p lower than 0.01): total cholesterol (-14.1%), low-density lipoprotein cholesterol (-16.8%), high-density lipoprotein (HDL) cholesterol (-11.3%), non-HDL cholesterol (-15.2%), glucose (-6.3%), and C-reactive protein (-14.2%). The diet also reduced fecal calprotectin (-21.0%, p=0.002) and zonulin levels (-14.9%, p=0.025) that are markers of gut inflammation and impaired barrier functions, respectively. Our study demonstrates pronounced beneficial effects of a microbiome restoration strategy based on the Non-Ind diet on metabolic markers of health. The findings provide valuable information for improving human health in modern societies. Ongoing analyses are exploring the mechanistic links between diet-induced changes in the gut microbiome and the physiological effects on the host.