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The gut microbiota is composed of the community of bacteria, archaea, fungi, and viruses that live in the human intestine and is unique to each individual. Diet can modulate the structure and function of the gut microbiota in ways that either increase or decrease disease risk. Findings of a new report detail the effects of a very-low-calorie diet on the gut microbiota, weight loss, and infection risk.

Following the absorption of most macronutrients (carbohydrates, fats, and proteins) and micronutrients (vitamins and minerals) present in food in the small intestine, undigested food travels to the large intestine where microbes metabolize any remaining nutrients. The amount and type of food consumed in the diet directly affect the amount and type of microbes that can flourish in the large intestine. Consuming a wide variety of foods in the diet supports a wide variety of microbes, while restricting certain foods or restricting caloric intake may reduce the abundance and diversity of the microbiota, a risk factor for disease.

The authors of the report recruited 80 females who had completed menopause and who had overweight or obesity. They randomized participants to complete a medically supervised weight-loss program or to maintain a stable weight for 16 weeks. Participants in the weight-loss program consumed a very-low-calorie diet (800 calories per day) for eight weeks, followed by four weeks of a conventional low-calorie diet and four weeks of a weight maintenance diet. The researchers sequenced DNA from the participants' gut microbiota to determine the number and type of microbes present. Finally, they collected gut microbiota samples from the baseline and 12-week timepoints from the participants who lost the most weight during the weight loss program. They transplanted these samples into germ-free mice, which lack a microbiota.

Participants in the weight-loss program lost an average of 14 percent of their body weight (about 27 pounds) after 12 weeks. A very-low-calorie diet reduced the abundance and diversity of microbes in the gut, but these changes were reversed when participants returned to a normal diet. Microbiota samples from the participants in the very-low-calorie diet intervention were enriched in Clostridioides difficile, a gastrointestinal pathogen (commonly referred to as “C. diff.”). This increase was associated with a reduction in the production of bile acids, which aid in dietary fat digestion and are protective against gastrointestinal pathogens. Mice that received a microbiota transplant from the very-low-calorie diet timepoint lost significantly more body weight due to changes in microbiota structure and reduced nutrient absorption, compared to mice that received a microbiota transplant from baseline.

This research highlights the importance of diet in the interplay between pathogenic and beneficial microbes in the gut microbiota.

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