By 2030, one in six people worldwide will be aged 60 years or older1. It is also true that frailty is a result of ageing and involves a decline in muscle strength, cognitive changes, and immune dysfunction. Inflammatory responses and oxidative stress resulting from an altered gut microbiome can negatively impact muscle function and cognition. While a variety of factors affect the aging process, inducing gut microbiome changes is unlikely to be the elixir of youth. However, there is an emerging interest in reversing aging-linked changes by influencing the microbiota-gut-brain axis2,3.

A new randomised controlled trial found that a prebiotic blend with inulin and fructo-oligosaccharides (FOS) for 12 weeks may improve cognition and is well tolerated in healthy volunteers over 60s, together with a protein and resistance exercise intervention4.

The prebiotic blend consisted of a mixture of inulin and FOS (7.5 g/d, comprising a minimum of 3.4 g of inulin and 3.5 g of FOS) and was compared to a placebo (maltodextrin). Study participants belonged to the TwinsUK cohort, which primarily consisted of healthy female twins (average age, 73; 78% female). Twin pairs were randomised, with one twin in each study arm. All participants received a protein and resistance exercise intervention, as the authors aimed to investigate whether the addition of a specific gut microbiome-targeted intervention could enhance the established muscle function improvements from a combined intervention with branched-chain amino acids and exercise.

There was no significant difference in muscle strength (the primary outcome measured by chair rise time, a marker of muscle strength). However, the prebiotic resulted in some improvement in cognition (a secondary outcome, measured with the number of errors in the Paired Associates Learning memory test) compared with the placebo. The authors argued that whether the improvement in cognition is clinically relevant remains to be seen. While a previous trial showed that the same prebiotic formulation improved frailty syndrome, the authors explained that the studied dose was likely insufficient to provide a meaningful response in muscle strength in a healthy volunteer cohort. It is also feasible that the inulin/FOS prebiotic is not the optimal combination for influencing muscle health.

The studied prebiotic was generally well tolerated and increased the relative abundance of Bifidobacterium as expected. In addition, forty microbiome features changed between baseline and the study end for participants taking the prebiotic, while only one changed in the placebo group.

Overall, the new study provides evidence for the beneficial effects of prebiotics on microbiota-brain systems in older adults for improving cognition. Further clinical evidence is needed to demonstrate that these findings are relevant for objective cognition outcomes and can be generalisable to younger age groups and the oldest old in healthy and clinical populations, particularly men who were underrepresented in the studied TwinsUK cohort. While awaiting more translational approaches to modulate the microbiota-gut-brain axis, it seems reasonable to promote a primarily unprocessed plant-based diet with some fermented foods for mental health maintenance in healthy older adults6.

 

References:

  1. World Health Organization. Ageing and health. 1 October 2024. Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health.
  2. Burokas A, Arboleya S, Moloney RD, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry. 2017; 82(7):472-487. doi: 10.1016/j.biopsych.2016.12.031.
  3. Aslam H, Lotfaliany M, So D, et al. Fiber intake and fiber intervention in depression and anxiety: a systematic review and meta-analysis of observational studies and randomized controlled trials. Nutr Rev. 2024; 82(12):1678-1695. doi: 10.1093/nutrit/nuad143.
  4. Lochlainn MN, Bowyer RCE, Moll JM, et al. Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial. Nat Commun. 2024; 15(1):1859. doi: 10.1038/s41467-024-46116-y.
  5. Buigues C, Fernández-Garrido J, Pruimboom L, et al. Effect of a prebiotic formulation on frailty syndrome: a randomized, double-blind clinical trial. Int J Mol Sci. 2016; 17(6):932. doi: 10.3390/ijms17060932.
  6. Schneider E, O’Riordan KJ, Clarke G, et al. Feeding gut microbes to nourish the brain: unraelling the diet-microbiota-gut-brain axis. Nat Metab. 2024; 6(8):1454-1478. doi: 10.1038/s42255-024-01108-6.