Authors
Priya Manna, Shayeri Chatterjee Ganguly, Arup Chatterjee, Banani Mondal, Aditi Maity, Srijita Chatterjee, Tanmoy Guria, Mainak Chakraborty
Published in
Metabolic brain disease. Volume 41. Issue 1. Jun 24, 2026. Epub Jun 24, 2026.
Abstract
Dementia is a growing global health concern, with limited therapeutic options. Treating dementia is a crucial but often overlooked part of neurological care for the elderly. The gut microbiota plays an essential role in the bidirectional interaction between the gut and the brain. Growing evidence suggests that gut microbes, which can influence neural development, modulate neurotransmission, and affect behaviour, may contribute to the development and pathophysiology of various neurodevelopmental, neuropsychiatric, and neurological disorders like dementia. This underscores the need for new interventions targeting the gut-brain axis(GBA). This review highlights the role and application of phytochemicals in treating dementia by modifying the GBA. We outline the harmful relationship between dementia and microbial dysbiosis, focusing on abnormal tryptophan- kynurenine metabolism, impaired SCFA synthesis, disruption of the BBB, and altered microglial activation states. Nevertheless, the potential of different phytochemicals, such as flavonoids, alkaloids, terpenoids, and polyphenols, to enhance neuroprotective metabolite production, restore microbial balance, regulate inflammatory signalling (e.g., NF- κb, Nrf 2, MAPK, and TLR 4), and improve synaptic plasticity via pathways like BDNF-CREB, is under investigation. Key bioactive compounds like berberine, resveratrol, and curcumin are being tested for their efficacy concerning molecular targets and outcomes in both preclinical and clinical models of cognitive decline. In addition to specific phytochemicals, probiotic and prebiotic synergistic approaches may enhance gut homeostasis and cognitive resilience, opening avenues for functional food- based treatments. Although promising, challenges to clinical application remain, such as low bioavailability, standardisation issues, and interindividual microbiome variability. This review emphasises prospects for precision nutrition and microbiome- targeted therapies in dementia, discusses translational barriers, and summarises recent data on phytochemical modulation of the GBA in dementia.
PMID:
42340489
Bibliographic data and abstract were imported from PubMed on 24 Jun 2026.
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