{"id":{"repo_id":"cork","oai_identifier":"oai:cora.ucc.ie:10468/18531"},"canonical_url":"https://search.dev.ndltd.org/etd/cork/oai:cora.ucc.ie:10468/18531","repository":{"repo_id":"cork","name":"University College Cork","base_url":"https://cora.ucc.ie/server/oai/request"},"display":{"title":"Modulation of the microbiota-gut-brain axis by fermented foods","abstract":"The gut harbours trillions of microbes that are involved in robust communication with the host. Various intrinsic and extrinsic factors modulate the composition of the gut microbiota. Over the past two decades seminal work on the impact of diet in shaping gut microbiota composition has resulted in dietary intervention strategies emerging as a means to modulate host-microbiota crosstalk. Fermented foods can be the focus of such dietary interventions and have recently gained increased attention as a potential source of microbiota-targeted therapeutics that can confer phenotypical benefits to the consumer. Fermented foods can be defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. Fermented foods can serve as conduits for potentially beneficial microbes, microbial metabolites and bioactives that can serve in a functional role to confer beneficial effects on the host. Given the shift in dietary practices across many countries towards a so-called ‘westernised’ diet and associated shifts in gut microbiota profiles, and the associated rising burden of non-communicable diseases, fermented foods represent a relevant gut microbiota–targeted intervention that can support host health in general, and in the context of this thesis, the microbiota-gut-brain axis. In this thesis, we first mined 820 fermented food metagenomes representing various substrate categories and different fermentation methodologies. We used in-silico approaches to identify fermented foods that harbour microbial pathways involved in the production of metabolites that are implicated in modulating gut-brain health. We next identified the role of food substrates in driving composition of microbial pathway richness implicated in gut-brain health. We also identified the fermentation methodologies employed to be a factor that was associated with the neuromodulatory potential of the microbial populations. Furthermore, we identified several fermented food-associated taxa that harbour genes involved in production of these neuroactive moieties, which can be harvested for gut-brain benefit. Following on from these foundational studies, we then employed untargeted metabolomics of specific fermented foods and unfermented controls to determine the relative influence of food substrate and fermentation status in shaping the metabolomic composition of fermented foods. We identified that food matrix, more so than fermentation status, shapes the metabolomic profile of fermented food. More specifically, to disentangle the effect of food fermentation from the food matrix in shaping gut microbiota profiles, we initially applied in-vitro batch fermentation systems that mimic the human distal colonic environment to a broad range of fermented foods belonging to various substrate categories. As noted, we show that food substrate rather than fermentation status per se influences gut microbiota composition, function and microbial metabolite production, with the exception of fermented vegetables-based foods such as kimchi and sauerkraut. We then moved to explore these substrate-dependent effects on host–microbiota crosstalk using murine models. Using fermented food and beverage supplementation alongside their unfermented counterparts, we observed that substrate-specific effects were the main drivers of gut microbiota composition, predicted function, and microbial metabolite profiles for beverages, whereas fermentation status differentially modulated these profiles for vegetable-based foods. Beyond characterising the impact of fermented foods on gut microbiota composition and function, we sought to understand the implications of these changes for the host. To answer this, we employed a high-fat-high-sugar model of a Westernised diet to determine whether fermented foods could differentially modulate the sequelae associated with diet-induced obesity. We found that substrate-specific responses, rather than fermentation status, were primarily responsible for attenuating neuroinflammatory signatures induced by the high-fat-high-sugar diet. This work collectively outlines the neuromodulatory potential of fermented food and comprehensively explores the impact of fermented foods, relative to unfermented controls, in modulating the microbiota-gut-brain axis. In doing so, it reveals food substrate as a critical factor that must be carefully considered in future studies aiming to investigate the effects of fermented foods on gut and brain health.","abstract_html":"The gut harbours trillions of microbes that are involved in robust communication with the host. Various intrinsic and extrinsic factors modulate the composition of the gut microbiota. Over the past two decades seminal work on the impact of diet in shaping gut microbiota composition has resulted in dietary intervention strategies emerging as a means to modulate host-microbiota crosstalk. Fermented foods can be the focus of such dietary interventions and have recently gained increased attention as a potential source of microbiota-targeted therapeutics that can confer phenotypical benefits to the consumer. Fermented foods can be defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. Fermented foods can serve as conduits for potentially beneficial microbes, microbial metabolites and bioactives that can serve in a functional role to confer beneficial effects on the host. Given the shift in dietary practices across many countries towards a so-called ‘westernised’ diet and associated shifts in gut microbiota profiles, and the associated rising burden of non-communicable diseases, fermented foods represent a relevant gut microbiota–targeted intervention that can support host health in general, and in the context of this thesis, the microbiota-gut-brain axis. In this thesis, we first mined 820 fermented food metagenomes representing various substrate categories and different fermentation methodologies. We used in-silico approaches to identify fermented foods that harbour microbial pathways involved in the production of metabolites that are implicated in modulating gut-brain health. We next identified the role of food substrates in driving composition of microbial pathway richness implicated in gut-brain health. We also identified the fermentation methodologies employed to be a factor that was associated with the neuromodulatory potential of the microbial populations. Furthermore, we identified several fermented food-associated taxa that harbour genes involved in production of these neuroactive moieties, which can be harvested for gut-brain benefit. Following on from these foundational studies, we then employed untargeted metabolomics of specific fermented foods and unfermented controls to determine the relative influence of food substrate and fermentation status in shaping the metabolomic composition of fermented foods. We identified that food matrix, more so than fermentation status, shapes the metabolomic profile of fermented food. More specifically, to disentangle the effect of food fermentation from the food matrix in shaping gut microbiota profiles, we initially applied in-vitro batch fermentation systems that mimic the human distal colonic environment to a broad range of fermented foods belonging to various substrate categories. As noted, we show that food substrate rather than fermentation status per se influences gut microbiota composition, function and microbial metabolite production, with the exception of fermented vegetables-based foods such as kimchi and sauerkraut. We then moved to explore these substrate-dependent effects on host–microbiota crosstalk using murine models. Using fermented food and beverage supplementation alongside their unfermented counterparts, we observed that substrate-specific effects were the main drivers of gut microbiota composition, predicted function, and microbial metabolite profiles for beverages, whereas fermentation status differentially modulated these profiles for vegetable-based foods. Beyond characterising the impact of fermented foods on gut microbiota composition and function, we sought to understand the implications of these changes for the host. To answer this, we employed a high-fat-high-sugar model of a Westernised diet to determine whether fermented foods could differentially modulate the sequelae associated with diet-induced obesity. We found that substrate-specific responses, rather than fermentation status, were primarily responsible for attenuating neuroinflammatory signatures induced by the high-fat-high-sugar diet. This work collectively outlines the neuromodulatory potential of fermented food and comprehensively explores the impact of fermented foods, relative to unfermented controls, in modulating the microbiota-gut-brain axis. In doing so, it reveals food substrate as a critical factor that must be carefully considered in future studies aiming to investigate the effects of fermented foods on gut and brain health.","abstract_has_math":false,"creators":["Balasubramanian, Ramya"],"institution":"University College Cork","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Cotter, Paul","Cryan, John"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025","date_published":"2025","updated_at":"2026-07-24T01:48:54Z","subjects":["Fermented food","Microbiota-gut-brain-axis","Metagenomics","Westernised diet"],"languages":["en"],"rights":["© 2025, Ramya Balasubramanian."],"rights_urls":["https://creativecommons.org/licenses/by-nc/4.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10468/18531","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cotter, Paul","Cryan, John"]},{"key":"dc:creator","label":"Author","values":["Balasubramanian, Ramya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-02-16T14:26:51Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2026-02-16T14:26:51Z"]},{"key":"dc:date.issued","label":"Date","values":["2025"]},{"key":"dc:publisher","label":"Institution","values":["University College Cork"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["PhD - Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Fermented food","Microbiota-gut-brain-axis","Metagenomics","Westernised diet"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["© 2025, Ramya Balasubramanian."]},{"key":"dc:rights.uri","label":"Rights URI","values":["https://creativecommons.org/licenses/by-nc/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10468/18531"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Controlled Access"]},{"key":"dc:description.abstract","label":"Abstract","values":["The gut harbours trillions of microbes that are involved in robust communication with the host. Various intrinsic and extrinsic factors modulate the composition of the gut microbiota. Over the past two decades seminal work on the impact of diet in shaping gut microbiota composition has resulted in dietary intervention strategies emerging as a means to modulate host-microbiota crosstalk. Fermented foods can be the focus of such dietary interventions and have recently gained increased attention as a potential source of microbiota-targeted therapeutics that can confer phenotypical benefits to the consumer. Fermented foods can be defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. Fermented foods can serve as conduits for potentially beneficial microbes, microbial metabolites and bioactives that can serve in a functional role to confer beneficial effects on the host. Given the shift in dietary practices across many countries towards a so-called ‘westernised’ diet and associated shifts in gut microbiota profiles, and the associated rising burden of non-communicable diseases, fermented foods represent a relevant gut microbiota–targeted intervention that can support host health in general, and in the context of this thesis, the microbiota-gut-brain axis. In this thesis, we first mined 820 fermented food metagenomes representing various substrate categories and different fermentation methodologies. We used in-silico approaches to identify fermented foods that harbour microbial pathways involved in the production of metabolites that are implicated in modulating gut-brain health. We next identified the role of food substrates in driving composition of microbial pathway richness implicated in gut-brain health. We also identified the fermentation methodologies employed to be a factor that was associated with the neuromodulatory potential of the microbial populations. Furthermore, we identified several fermented food-associated taxa that harbour genes involved in production of these neuroactive moieties, which can be harvested for gut-brain benefit. Following on from these foundational studies, we then employed untargeted metabolomics of specific fermented foods and unfermented controls to determine the relative influence of food substrate and fermentation status in shaping the metabolomic composition of fermented foods. We identified that food matrix, more so than fermentation status, shapes the metabolomic profile of fermented food. More specifically, to disentangle the effect of food fermentation from the food matrix in shaping gut microbiota profiles, we initially applied in-vitro batch fermentation systems that mimic the human distal colonic environment to a broad range of fermented foods belonging to various substrate categories. As noted, we show that food substrate rather than fermentation status per se influences gut microbiota composition, function and microbial metabolite production, with the exception of fermented vegetables-based foods such as kimchi and sauerkraut. We then moved to explore these substrate-dependent effects on host–microbiota crosstalk using murine models. Using fermented food and beverage supplementation alongside their unfermented counterparts, we observed that substrate-specific effects were the main drivers of gut microbiota composition, predicted function, and microbial metabolite profiles for beverages, whereas fermentation status differentially modulated these profiles for vegetable-based foods. Beyond characterising the impact of fermented foods on gut microbiota composition and function, we sought to understand the implications of these changes for the host. To answer this, we employed a high-fat-high-sugar model of a Westernised diet to determine whether fermented foods could differentially modulate the sequelae associated with diet-induced obesity. We found that substrate-specific responses, rather than fermentation status, were primarily responsible for attenuating neuroinflammatory signatures induced by the high-fat-high-sugar diet. This work collectively outlines the neuromodulatory potential of fermented food and comprehensively explores the impact of fermented foods, relative to unfermented controls, in modulating the microbiota-gut-brain axis. In doing so, it reveals food substrate as a critical factor that must be carefully considered in future studies aiming to investigate the effects of fermented foods on gut and brain health."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Modulation of the microbiota-gut-brain axis by fermented foods"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cotter, Paul","Cryan, John"],"dc:creator":["Balasubramanian, Ramya"],"dc:date.accessioned":["2026-02-16T14:26:51Z"],"dc:date.available":["2026-02-16T14:26:51Z"],"dc:date.issued":["2025"],"dc:description":["Controlled Access"],"dc:description.abstract":["The gut harbours trillions of microbes that are involved in robust communication with the host. Various intrinsic and extrinsic factors modulate the composition of the gut microbiota. Over the past two decades seminal work on the impact of diet in shaping gut microbiota composition has resulted in dietary intervention strategies emerging as a means to modulate host-microbiota crosstalk. Fermented foods can be the focus of such dietary interventions and have recently gained increased attention as a potential source of microbiota-targeted therapeutics that can confer phenotypical benefits to the consumer. Fermented foods can be defined as foods or beverages produced through controlled microbial growth, and the conversion of food components through enzymatic action. Fermented foods can serve as conduits for potentially beneficial microbes, microbial metabolites and bioactives that can serve in a functional role to confer beneficial effects on the host. Given the shift in dietary practices across many countries towards a so-called ‘westernised’ diet and associated shifts in gut microbiota profiles, and the associated rising burden of non-communicable diseases, fermented foods represent a relevant gut microbiota–targeted intervention that can support host health in general, and in the context of this thesis, the microbiota-gut-brain axis. In this thesis, we first mined 820 fermented food metagenomes representing various substrate categories and different fermentation methodologies. We used in-silico approaches to identify fermented foods that harbour microbial pathways involved in the production of metabolites that are implicated in modulating gut-brain health. We next identified the role of food substrates in driving composition of microbial pathway richness implicated in gut-brain health. We also identified the fermentation methodologies employed to be a factor that was associated with the neuromodulatory potential of the microbial populations. Furthermore, we identified several fermented food-associated taxa that harbour genes involved in production of these neuroactive moieties, which can be harvested for gut-brain benefit. Following on from these foundational studies, we then employed untargeted metabolomics of specific fermented foods and unfermented controls to determine the relative influence of food substrate and fermentation status in shaping the metabolomic composition of fermented foods. We identified that food matrix, more so than fermentation status, shapes the metabolomic profile of fermented food. More specifically, to disentangle the effect of food fermentation from the food matrix in shaping gut microbiota profiles, we initially applied in-vitro batch fermentation systems that mimic the human distal colonic environment to a broad range of fermented foods belonging to various substrate categories. As noted, we show that food substrate rather than fermentation status per se influences gut microbiota composition, function and microbial metabolite production, with the exception of fermented vegetables-based foods such as kimchi and sauerkraut. We then moved to explore these substrate-dependent effects on host–microbiota crosstalk using murine models. Using fermented food and beverage supplementation alongside their unfermented counterparts, we observed that substrate-specific effects were the main drivers of gut microbiota composition, predicted function, and microbial metabolite profiles for beverages, whereas fermentation status differentially modulated these profiles for vegetable-based foods. Beyond characterising the impact of fermented foods on gut microbiota composition and function, we sought to understand the implications of these changes for the host. To answer this, we employed a high-fat-high-sugar model of a Westernised diet to determine whether fermented foods could differentially modulate the sequelae associated with diet-induced obesity. We found that substrate-specific responses, rather than fermentation status, were primarily responsible for attenuating neuroinflammatory signatures induced by the high-fat-high-sugar diet. This work collectively outlines the neuromodulatory potential of fermented food and comprehensively explores the impact of fermented foods, relative to unfermented controls, in modulating the microbiota-gut-brain axis. In doing so, it reveals food substrate as a critical factor that must be carefully considered in future studies aiming to investigate the effects of fermented foods on gut and brain health."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/10468/18531"],"dc:language.iso":["en"],"dc:publisher":["University College Cork"],"dc:rights":["© 2025, Ramya Balasubramanian."],"dc:rights.uri":["https://creativecommons.org/licenses/by-nc/4.0/"],"dc:subject":["Fermented food","Microbiota-gut-brain-axis","Metagenomics","Westernised diet"],"dc:title":["Modulation of the microbiota-gut-brain axis by fermented foods"],"dc:type":["Doctoral thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["PhD - Doctor of Philosophy"]},"updated_at":"2026-07-24T01:48:54Z"}