Microbiota Stability and Gastrointestinal Tolerance in Response to a High-Protein Diet with and without a Prebiotic, Probiotic, and Synbiotic: A Randomized, Double-Blind, Placebo-Controlled Trial in Older Women

J Acad Nutr Diet. 2020 Apr;120(4):500-516.e10. doi: 10.1016/j.jand.2019.12.009.


Background: Higher protein intakes may help reduce sarcopenia and facilitate recovery from illness and injury in older adults. However, high-protein diets (HPDs) including animal-sourced foods may negatively perturb the microbiota, and provision of probiotics and prebiotics may mitigate these effects.

Objective: The aim of this study was to examine the effects of HPD, with and without a probiotic and/or prebiotic, on gut microbiota and wellness in older women.

Design: We conducted an 18-week, double-blind, placebo-controlled, crossover study.

Participants/setting: Participants were healthy, older women (mean age±standard deviation=73.7±5.6 years; n=26) recruited from Florida.

Intervention: Participants received a weight-maintenance HPD for 2-week periods and the following, in random order: HPD alone (1.5 to 2.2 g/kg/day protein); HPD plus multistrain probiotic formulation (1.54×109Bifidobacterium bifidum HA-132, 4.62×109Bifidobacterium breve HA-129, 4.62×109Bifidobacterium longum HA-135, 4.62×109Lactobacillus acidophilus HA-122, and 4.62×109Lactobacillus plantarum HA-119), HPD plus prebiotic (5.6 g inulin), and HPD plus synbiotic (probiotic plus inulin), separated by 2-week washouts. Stools were collected per period for quantitative polymerase chain reaction (strain recovery) and 16S ribosomal RNA gene amplicon sequencing analyses (microbiota profile). Measures of gastrointestinal and general wellness were assessed.

Main outcome measures: Microbiota composition and probiotic strain recovery were measured.

Statistical analyses: Microbiota composition was analyzed by Wilcoxon signed-rank test and t test. Secondary outcomes were analyzing using generalized linear mixed models.

Results: The microbiota profile demonstrated relative stability with the HPD; representation of Lactobacillus, Lactococcus, and Streptococcus were enhanced, whereas butyrate producers, Roseburia and Anaerostipes, were suppressed. Lactococcus was suppressed with synbiotic vs other HPD periods. Recovery was confirmed for all probiotic strains. Indicators of wellness were unchanged, with the exception of a minimal increase in gastrointestinal distress with inulin. Fat-free mass increased from baseline to study end.

Conclusions: An HPD adhering to the recommended acceptable macronutrient distribution ranges maintains wellness in healthy older women and exerts minor perturbations to the microbiome profile, a group that may benefit from a higher protein intake. ClinicalTrials.gov ID: NCT #02445560.

Trial registration: ClinicalTrials.gov NCT02445560.

Keywords: High-protein diet; Microbiome; Older adult; Prebiotic; Probiotic.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Over Studies
  • Diet, High-Protein / methods*
  • Double-Blind Method
  • Elder Nutritional Physiological Phenomena
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Tract / microbiology*
  • Healthy Volunteers
  • Humans
  • Prebiotics / administration & dosage*
  • Probiotics / administration & dosage*
  • Synbiotics / administration & dosage*


  • Prebiotics

Associated data

  • ClinicalTrials.gov/NCT02445560