Microbiota magic: illuminating the impact of faecal transplants on cognitive function

Abstract

The gut microbiome influences not only digestive processes but also systemic metabolism, including brain function, leading to increased interest in microbiome-targeted interventions. Faecal Microbiota Transplantation (FMT) has emerged as an experimental treatment, primarily for gastrointestinal disorders, with preliminary evidence suggesting possible cognitive benefits. However, no placebo-controlled, double-blinded trials have investigated its effects on cognition in either cognitively healthy individuals or those with Mild Cognitive Impairment (MCI), a transitional stage between normal cognitive ageing and dementia. This thesis aimed to explore preliminary effects of FMT on cognitive function in individuals experiencing Irritable Bowel Syndrome (IBS), with and without comorbid MCI, while investigating potential gut-brain axis pathways involved in any observed cognitive change, and to assess feasibility of FMT studies in these populations. To address this, we conducted two randomised, placebo-controlled, double-blinded pilot studies in people with IBS. One trial enrolled cognitively healthy individuals (N = 16), and the other enrolled those with comorbid MCI (N = 9). Cognitive function, mood, and biological response were measured at baseline, and 1, 3, and 6 months after participants received a single dose of rectal FMT or placebo, with an additional 12-month follow-up in the healthy cohort. Cognitive outcomes were assessed with the Cambridge Neuropsychological Automated Test Battery (CANTAB), the Montreal Cognitive Assessment (MoCA), and the California Verbal Learning Test-II (CVLT-II). Biological analyses included metagenomic sequencing of gut microbiota, and the quantification of microbial metabolites (short-chain fatty acids), tryptophan-kynurenine metabolism, and cytokines. Furthermore, mood and IBS symptom severity were also assessed via questionnaires. At the group level, no significant effects of FMT were observed on cognition, mood, IBS symptoms, microbiota composition, or any plasma analytes. However, two FMT recipients in the MCI cohort showed significant changes in gut microbial composition after FMT. In one case, this was accompanied by a marked cognitive improvement, alongside an increase in Firmicutes/Bacteroidota ratio. Furthermore, we found a treatment independent positive relationship between gut microbial alpha diversity and cognitive function across both studies. In conclusion, single-dose enema FMT does not appear to induce cognitive changes in people with IBS, with or without MCI. Nevertheless, individual cases of benefit and the consistent link between microbial diversity and cognition suggest that future studies should investigate personalised approaches and strategies targeting gut microbiota diversity.

Date of Thesis submission	2025
Original language	English
Awarding Institution	Western Sydney University
Sponsors	Australian Government Research Training Program Scholarship
Supervisor	Vincent Ho (Supervisor), Tara Roberts (Supervisor), Genevieve Steiner-Lim (Supervisor) & Slade Jensen (Supervisor)