Novel Insights into the impact of dietary components on the microbiota–gut–brain axis in humans

dc.check.chapterOfThesis5-year embargo on entire thesis.
dc.check.date2031-12-31
dc.contributor.advisorCryan, John
dc.contributor.advisorClarke, Gerard
dc.contributor.authorFerri, Aimoneen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderPrivate philanthropy donationen
dc.date.accessioned2026-09-28T11:20:59Z
dc.date.available2026-09-28T11:20:59Z
dc.date.issued2026-01-15
dc.date.submitted2026-01-15
dc.description.abstractMental health disorders and cognitive decline represent global health burdens, with rising prevalence across age groups, and therapeutic options are either limited or unsatisfactory. Diet is increasingly recognised as a modifiable factor affecting brain health, acting in part through the microbiota-gut-brain axis, the bidirectional communication network linking the trillions of microorganisms inhabiting our gut to the central nervous system. Despite growing evidence for diet-brain relationships, the mechanisms through which specific dietary components influence cognitive function, mood, and stress-related outcomes in healthy adults remain incompletely understood, and both methodological limitations in dietary assessment and analytical approaches have constrained progress in this field. Importantly, studying young, healthy individuals offers a valuable preventive window: most mental health and neurodegenerative conditions develop gradually over years, and the biological and behavioural changes that precede clinical onset may be more sensitive to dietary modification before these conditions are already manifest. This thesis examined these relationships through four complementary studies which included mechanistic, observational, interventional, and methodological approaches to study the diet-brain health relationship. Chapter 2 examined the effects of habitual coffee intake on the microbiota-gut-brain axis using a cross-sectional study and a randomized controlled trial design, including a washout period, and then the reintroduction of caffeinated or decaffeinated coffee in habitual coffee drinkers. Coffee abstinence produced reversible shifts in gut microbiome composition and metabolomic profiles toward those observed in non-coffee drinkers, which were restored upon reintroduction regardless of caffeine content, supporting a broad effect of the coffee food matrix in shaping the microbiota-gut-brain axis. Caffeinated and decaffeinated coffee produced distinct psychological profiles, with anxiety and sustained attention more closely associated with caffeine and improvements in episodic memory and sleep quality more associated with the decaffeinated condition, pointing to unique domain-specific effects of coffee on brain function. Chapter 3 investigated the relationship between habitual dietary fibre intake and brain-related outcomes in a cross-sectional study of 220 young healthy adults. Higher fibre intake was selectively associated with lower depressive symptoms and better pattern recognition memory performance, with aspects of socioeconomic status and physical activity emerging as relevant confounders. These selective associations are consistent with the idea that diet-brain relationships in healthy populations are subtle, specific but detectable with a comprehensive study design. Chapter 4 investigated the effects of an 8-week four-arm dietary randomized controlled trials aimed at increasing fibre intake, fermented food intake, their combination, or an active control on mood, cognition, and stress reactivity in healthy adults with habitually low fibre intake. Frequentist analyses did not identify statistically significant differences between arms, but Bayesian multivariate joint models provided support for improvements in depressive symptoms specifically in the combined dietary arm, with converging directional evidence for broader psychological wellbeing in both the combined and fermented food arms. These findings suggest a potential synergistic effect of fibre and fermented foods on the mood related outcomes identified in Chapter 3 and demonstrate the value of including Bayesian methods for better characterising effect magnitude and uncertainty in these scenarios. Chapter 5 addressed a key methodological gap of the field by developing and validating a Fermented Food Intake Questionnaire (FFIQ), the first comprehensive dietary assessment tool designed to capture habitual fermented food consumption across multiple food categories in English-speaking countries. The FFIQ demonstrated good validity against multiple 24-hour dietary recalls and good test-retest reliability, providing a resource for nutritional epidemiology and gut microbiome research examining fermented food exposure. Finally, a pre-registered structural equation modelling protocol designed to investigate the relationships between dietary patterns, and brain health outcomes in a large online sample of American adults is presented in the Appendix, as a methodological foundation for future research to improve inferences in complex diet and brain health research. Collectively, the findings presented in this thesis show that diet can exert selective, biologically plausible effects on multiple aspects of brain health in healthy adults, and that detecting these effects requires matched measurement precision, biological characterisation, and analytical approaches suited to investigate the complexity of dietary exposures. The validated tools and methodological advances presented here contribute to the growing infrastructure needed to advance diet-brain research toward personalised, evidence-based dietary guidance for brain health.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationFerri, A. 2026. Novel Insights into the impact of dietary components on the microbiota–gut–brain axis in humans. PhD Thesis, University College Cork.
dc.identifier.endpage453
dc.identifier.urihttps://hdl.handle.net/10468/19340
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Research Centres Programme::Phase 2/12/RC/2273_P2/IE/APC_Phase 2/
dc.rights© 2026, Aimone Ferri.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectMicrobiota-gut-brain axisen
dc.subjectDieten
dc.subjectNeuroscienceen
dc.subjectMental healthen
dc.subjectCognitionen
dc.titleNovel Insights into the impact of dietary components on the microbiota–gut–brain axis in humans
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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