Caloric restriction disrupts the microbiota and colonization resistance

Abstract

Diet is a major factor that shapes the gut microbiome 1 , but the consequences of diet-induced changes in the microbiome for host pathophysiology remain poorly understood. We conducted a randomized human intervention study using a very-low-calorie diet (NCT01105143). Although metabolic health was improved, severe calorie restriction led to a decrease in bacterial abundance and restructuring of the gut microbiome. Transplantation of post-diet microbiota to mice decreased their body weight and adiposity relative to mice that received pre-diet microbiota. Weight loss was associated with impaired nutrient absorption and enrichment in Clostridioides difficile, which was consistent with a decrease in bile acids and was sufficient to replicate metabolic phenotypes in mice in a toxin-dependent manner. These results emphasize the importance of diet-microbiome interactions in modulating host energy balance and the need to understand the role of diet in the interplay between pathogenic and beneficial symbionts.

Metabolic reconstitution by a gnotobiotic microbiota varies over the circadian cycle

“…We are also keen to point out the more general limitations of our observations: only one gnotobiotic microbiota and one SPF microbiota were analyzed, and our conclusions pertain exclusively to these. We in no way exclude the possibility that some microbiota constituents or conformations can influence host energy expenditure (Halatchev et al, 2019) and/or body composition (Ridaura et al, 2013;von Schwartzenberg et al, 2021;Turnbaugh et al, 2006). In addition, it should be noted that indirect calorimetry is an inherently noisy data type, and small differences in daily energy expenditure are impossible to resolve via this technique (Corrigan et al, 2020;Fernández-Verdejo et al, 2019).…”

Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition

“…As noted above, however, cooperative microbial communities also tend to be low-diversity and more susceptible to the invasion of novel species. Indeed, deliberate caloric restriction in humans was recently shown to reduce colonization resistance, leading to the expansion of C. difficile 44 . The fecal microbiota of malnourished children been found to include an overabundance of oral and upper airway bacteria, as well as a chronic overabundance of pathogens 12 ; these patterns are consistent with reduced colonization resistance of the microbial ecosystem during child malnutrition, and we suggest this might be driven in part by destabilizing cooperative growth.…”

Effects of anti-aging interventions on intestinal microbiota

“…Transplantation of post-diet microbiota to mice decreased their body weight and was enriched with the enteric pathogen Clostridioides difficile . 43 …”