Caloric restriction disrupts the microbiota and coloniation resistance

von Schwartzenberg R, Bisanz J, Lyalina S, et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 2021; 595: 272–277. doi: 10.1038/s41586-021-03663-4

Diet is a known factor that influences the gut microbiome, but the consequences that extreme caloric restriction induces on the microbiome for host pathophysiology remain poorly understood. To address this knowledge gap, the authors conducted a randomised human intervention study using a very-low-calorie diet (VLCD). Eighty post-menopausal women who were overweight or obese were randomised into two groups. Women either followed a medically supervised meal replacement regime (approximately 800 kilocalories daily) or maintained their weight for the duration of the study. Regular stool samples were collected from both groups. Results indicated a decrease in bacterial colonisation, an increase in bacterial diversity and a reduction in short chain fatty acids produced by the gut microbiome during VLCD. Transplantation of the human post-VLCD gut microbiota into mice indicated that dietary perturbations to the gut microbiome contribute to weight loss. Mice experienced a decrease in their body weight and adiposity, relative to mice that received pre-diet microbiota despite no differences in caloric intake across groups. Further investigation showed that C. difficile levels increased in the post-diet mice. Addition of C. difficile spores to post-VLCD stool led to increased and sustained weight loss over the duration of the experiment. von Schwartzenberg et al concluded that the increase in C. difficile is due to decreased fat consumption and consequently a reduction in bile acids, which modulates the growth and germination of C. difficile. These results highlight the importance of diet–microbiome interactions in modulating host energy balance and the importance of understanding the role of diet in the interplay between pathogenic and beneficial symbionts.

Single cell sequencing creates a dynamic cellular map of GI tract development

Elmentaite R, Kumasaka N, Roberts K, et al. Cells of the human intestinal tract mapped across space …