Effects of underfeeding and oral vancomycin on gut microbiome and nutrient absorption in humans.
Administration, Oral
Adolescent
Adult
Caloric Restriction
Cross-Over Studies
Diet
Double-Blind Method
Energy Metabolism
/ drug effects
Feces
/ microbiology
Female
Gastrointestinal Microbiome
/ drug effects
Humans
Intestinal Absorption
/ drug effects
Male
Malnutrition
/ metabolism
Middle Aged
Nutrients
/ pharmacokinetics
Vancomycin
/ administration & dosage
Verrucomicrobia
/ isolation & purification
Young Adult
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
15
02
2019
accepted:
13
02
2020
pubmed:
3
4
2020
medline:
23
7
2020
entrez:
3
4
2020
Statut:
ppublish
Résumé
Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. The first phase was a randomized cross-over dietary intervention in which all participants underwent in random order 3 d of over- and underfeeding. The second was a randomized, double-blind, placebo-controlled pharmacologic intervention using oral vancomycin or matching placebo (NCT02037295). Twenty-seven volunteers (17 men and 10 women, age 35.1 ± 7.3, BMI 32.3 ± 8.0), who were healthy other than having impaired glucose tolerance and obesity, were enrolled and 25 completed the entire trial. The primary endpoints were the effects of dietary and pharmacological intervention on stool calorie loss. We hypothesized that stool calories expressed as percentage of caloric intake would increase with underfeeding compared with overfeeding and increase during oral vancomycin treatment. Both primary endpoints were met. Greater stool calorie loss was observed during underfeeding relative to overfeeding and during vancomycin treatment compared with placebo. Key secondary endpoints were to evaluate the changes in gut microbial community structure as evidenced by amplicon sequencing and metagenomics. We observed only a modest perturbation of gut microbial community structure with under- versus overfeeding but a more widespread change in community structure with reduced diversity with oral vancomycin. Increase in Akkermansia muciniphila was common to both interventions that resulted in greater stool calorie loss. These results indicate that nutrient absorption is sensitive to environmental perturbations and support the translational relevance of preclinical models demonstrating a possible causal role for the gut microbiome in dietary energy harvest.
Identifiants
pubmed: 32235930
doi: 10.1038/s41591-020-0801-z
pii: 10.1038/s41591-020-0801-z
doi:
Substances chimiques
Vancomycin
6Q205EH1VU
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
589-598Subventions
Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA227232
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK098722
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122593
Pays : United States
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