Gut Microbiome Linked to Early Brain Ageing

A new study links patterns of accelerated brain ageing in young and middle-aged adults to specific gut bacteria and blood metabolites, offering a potential early window into cognitive and mood-related decline. The research, involving nearly 1,500 adults, found that individuals whose brains appeared older than their chronological age performed worse on cognitive tests and reported significantly more symptoms of depression.

Higher Brain Ageing Index scores correlated with worse performance on working memory and executive function tests. The index, or BAI, is calculated as the difference between a person's estimated brain age, derived from fMRI scans, and their actual chronological age. Across the cohorts, a higher BAI was consistently associated with increased symptoms of depression.

Gut metabolites and microbes associated with accelerated brain ageing

Elevated BAI links to specific gut bacteria, fat molecules, cholesterol-related compounds, and lower estetrol levels, tied to immune and brain function pathways. The analysis connected a higher BAI with increased levels of ceramides, 24-hydroxycholesterol, and dicarboxylic acids. It also showed an inverse association with estetrol, a naturally occurring oestrogen hormone.

Pathway enrichment analyses linked the identified metabolites to immune function, blood vessel function, brain cell communication, and cellular energy production. The structural brain changes linked to elevated BAI involved the posterior cingulate and medial frontal regions, areas critical for memory and self-referential thought.

Methods reveal how brain and gut data were connected across cohorts

Researchers used fMRI scans from three adult groups and stool samples in one cohort to link brain ageing markers with microbial and metabolic profiles. The study examined resting-state fMRI scans from 1,462 healthy adults aged 18 to 65. Participants were divided into three cohorts: a discovery group of 674, a replication group of 444, and an independent group of 344.

The Brain Ageing Index was calculated using Bayesian ridge regression and a 100-region Schaefer parcellation network. In the independent cohort, 182 individuals provided stool samples for microbiome and metabolomic analysis. Scientists used a multi-view sparse partial least squares method to link BAI data with gut microbial and metabolic profiles. The study design was cross-sectional, which limits causal inferences about the directionality of the gut-brain relationship.

Experts suggest gut-brain axis as target for early brain health support

Findings indicate the microbiome could be intervened upon to support brain health before neurological symptoms appear. The study's senior author, Dr. Arpana Church, co-director of the Goodman-Luskin Microbiome Center at UCLA Health, explained the significance. Dr. Church said: "Brain aging doesn't suddenly begin when we get older, but the biological signals may be detectable decades earlier."

The work suggests the gut microbiome could be a target for early intervention to support brain health. The study suggests future potential for probiotics, dietary changes, or therapeutics targeting the gut-brain axis to preserve executive function before neurological disease onset.