Can the modulation of the gut microbiome using a prebiotic improve muscle function and cognition?

By Pooja Toshniwal PahariaMar 4 2024Reviewed by Danielle Ellis, B.Sc.

In a recent study published in Nature Communications, researchers examined the efficacy of a prebiotic in improving muscular and cognitive performance vs. a placebo among elderly individuals.

Background

As the world's population ages, age-related disorders such as muscle loss and cognitive impairment become more common. Researchers and physicians must acknowledge cognitive changes as part of healthy aging. Exercise can help reduce muscle loss, although elderly individuals may struggle. Interventions with physical and mental advantages are required.

According to recent studies, alterations in the gut microbiota might influence muscle physiology and cognitive function, potentially altering anabolic resistance in older muscles and cognition. Prebiotics are associated with improved health in older individuals.

About the study

In the present study, researchers explored the role of gut microbiota regulation in enhancing cognition and muscular function benefits from protein supplementation and exercise in elders.

The team conducted the PRebiotic and PrOtein on Muscle in Older Twins (PROMOTe) trial remotely using video visits, online surveys, cognitive tests, and the sending of equipment and biological samples. Participants were aged ≥60 years and had a low protein consumption of <1.0 g per kg weight per day, as established by the TwinsUK group.

The team excluded participants with severe food allergies, ongoing or recent antibiotic use, protein supplementation, prebiotics and probiotics, and advanced renal disease. They also excluded individuals with a weight reduction of ≥5.0% of body weight in the previous year, major surgery or injury that could alter physical functions, and current participation in other interventional trials.

The team randomized twin pairs to receive either a placebo (7.5g maltodextrin) or a prebiotic (intervention, 3.4 g inulin and 3.5 g fructo-oligosaccharides) daily for 12 weeks. They provided all individuals with 3.3g of branched-chain-type amino acid (BCAA) supplementation and resistance training. The primary objective was to reduce chair rise time (the time required to do five chair raises without using arms). Secondary outcomes included the cognitive battery factor score, the SPPB score (including chair rise time and gait speed), grip strength, gait speed, physical activity levels assessed using the International Physical Activity Questionnaire (IPAQ), and the Simplified Nutritional Assessment Questionnaire (SNAQ) appetite scale.

The participants completed the Short Physical Performance Battery (SPPB) remotely, including chair rise time and handgrip strength evaluations with a dynamometer with real-time instructions from a qualified researcher. The participants provided stool samples to extract microbial DNA for gut microbiota characterization by shotgun metagenomic sequencing. The CANTAB battery includes cognitive tests for executive function, spatial working memory, and memory. The team evaluated three days of food diary data. They conducted intention-to-treat (ITT), per-protocol (PP), and heritability analyses.

Results

Of 626 eligible individuals, 72 were successfully recruited (36 twin pairs). The participants had a mean age of 73 and were 78% female. There were more moderate adverse effects (like abdominal bloating) in the intervention group compared to the placebo group; however, the team found no compliance-related differences, indicating that the supplements were generally well accepted. In either arm, no participants stated gastrointestinal side effects as a cause for non-adherence to the research intervention. No critical adverse effects occurred.

There were no significant changes in findings between the PP and ITT models. The team found no significant differences between the study groups concerning primary or secondary outcomes. The intervention group outperformed the placebo group in terms of cognition first-factor scores. Furthermore, the specific cognition assessment paired associations learning showed considerably fewer errors in the intervention group than in the placebo group.

Using Bray-Curtis dissimilarity, twin pairs' microbiotas were considerably more similar to the microbiota compositions of unrelated people at baseline and the conclusion of the research. The alpha and beta diversity assessments revealed no significant changes between the prebiotic and placebo groups. Compositional bias-adjusted linear modeling controlling for twin- and arm-pair-associated effects showed 144 microbiota characteristics, including 109 microbiome taxa, 33 microbe functions, richness, and Faith's phylogenetic diversity strongly associated with chair rise time.

Correlation analysis of changes in microbiota characteristics and chair rise times throughout the research intervention period demonstrated a link between chair rise duration improvement and changes in richness, Shannon diversity, and Faith's diversity. The study found 11 significant differences between the prebiotic and placebo groups, with the prebiotic group having higher levels of Bifidobacterium, Actinobacteria, Firmicutes, Bacteroidetes, and Phocea massiliensis. Eight microbiome traits were associated with cognitive capacity, including an increase in actinobacteria and improvements in cognition component scores.

Conclusion

Overall, the study found that gut microbiome manipulations can enhance cognition in elders, demonstrating the viability of remote trials for older adults. The prebiotic intervention, which was well tolerated and altered gut microbiota, increased the quantity of Bifidobacterium. However, there were no significant changes in chair rise times between the study groups. Future larger-scale research should explore the possibility of gut microbiome-targeted therapies to overcome age-related anabolic resistance.