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Studies show role of human gut microbiome in nutrient absorption

Researchers in the NIDDK’s intramural research program, partnering with scientists at academic institutions in the United States and Germany, found that changes in people’s gut microbiomes, due to diet or antibiotic use, directly altered nutrient absorption, backing up results from animal models and indirect associations in prior human studies. Decades of research, mainly in animal models, have illustrated how influential gut microbes can be in supplementing individuals’ metabolic machinery and determining how much nutrition is extracted from the diet. Human studies in this area have produced similar but indirect associations. For example, one study showed that underfeeding (ingesting less calories than required to maintain current weight) remodeled the microbiome and reduced nutrient absorption, but it was unclear if the effects on nutrient absorption were directly caused by changes in the microbiome.

Scientists wished to test whether there was a causal relationship between human gut microbes and nutrient absorption in a controlled feeding study in which the participants’ microbiomes were altered by diet or antibiotics. This study design provided accurate assessment of dietary intake, with adult men and women, some of whom had obesity or impaired glucose tolerance, staying at the NIH Clinical Research Unit at the Phoenix Indian Medical Center in Arizona throughout the study period of 31 days. During this time, they were given prepared meals, which were closely monitored to ensure 95 percent of foods were consumed, and had samples taken. For the first phase of the study, all participants were overfed and underfed the same foods for 3 days each, in random order, with a weight-maintaining diet provided in between. In the second phase, they were fed a weight-maintaining diet and given either the oral antibiotic vancomycin or a placebo pill. The scientists measured nutrient absorption by monitoring the calories passed in stool and urine samples. They also tracked the activity and composition of the gut microbiome by measuring plasma biomarkers of host and microbial metabolism and the number and types of gut bacteria present in the stool. Both underfeeding and antibiotics reduced nutrient absorption (i.e., more nutrients were lost in the stool). In the case of underfeeding, the scientists attributed this to lower nutrient availability for gut microbial metabolism. These short-term dietary changes altered the composition of gut microbes slightly, and antibiotic treatment changed it more dramatically, with a loss of diversity in gut microbial species, which may have hampered the metabolic capacity of the remaining gut microbes. In fact, a marker for microbial metabolism was lower in the people who were underfed or treated with the antibiotic, pointing to reduced nutrient metabolism by the microbiome under these conditions.

This study offers high-quality evidence for a direct role of gut microbes in the amount of nutrients a given person can extract from their food, including the impact of environmental factors such as diet and antibiotic use. These findings also bolster the validity of animal models in which similar results were found. Additional, larger human studies are needed to determine the potential therapeutic implications of this research.

Basolo A, Hohenadel M, Ang QY,…Krakoff J. Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans. Nat Med 26: 589-598, 2020.