Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 CellsOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study tested how very low-carbohydrate ketogenic diets change the gut microbiome and host immunity, and whether those effects differ from ordinary high-fat diets. It combined a controlled human feeding trial with follow-up mouse and laboratory experiments. Human stool was profiled by 16S rRNA sequencing, metagenomics, and NMR metabolomics. Mice were fed graded carbohydrate diets, and germ-free mice received bacterial mono-colonizations and human microbiome transplants to test downstream immune effects.
Who was studied?
The human arm was an inpatient crossover study of 17 overweight or class I obese, non-diabetic adult men. Each ate a baseline diet for 4 weeks, then a ketogenic diet for 4 weeks, with stool collected in the final week of each phase. Mouse work used C57BL/6J mice fed low-fat, high-fat, and ketogenic diets over weeks to months. Further experiments used germ-free mice, in vitro bacterial cultures, and human donor stool incubations with the ketone body beta-hydroxybutyrate.
What were the most important findings?
The ketogenic diet shifted the human microbiome distinctly from high-fat diets, with 19 genera differing between phases and bifidobacteria showing the greatest decrease. In mice, the ketogenic diet reversed the high-fat pattern, lowering Firmicutes and Actinobacteria while raising Bacteroidetes. The ketone body beta-hydroxybutyrate directly and dose-dependently inhibited growth of Bifidobacterium, including a strain isolated from the human cohort, through a pH-dependent mechanism. Bifidobacteria induce pro-inflammatory intestinal Th17 cells, and the ketogenic diet, by depleting these bacteria, reduced Th17 cell levels in the small intestine of mice.
What are the greatest implications of this study?
The work shows that ketogenic diets act partly through the gut microbiome, using ketone bodies as chemical signals that reshape which bacteria thrive. Lowering bifidobacteria in turn dampens intestinal Th17 immune cells. This links a dietary intervention to a specific host-microbe-immune pathway that could matter for inflammatory conditions. The human arm was small, all-male, and short-term, and luminal ketone concentrations were far lower than doses used in culture, so the exact in-body mechanism needs further study.