Gut Microbiota–Host Metabolic Networks in Alzheimer’s Disease: From Pathological Mechanisms to Modulation by Traditional Chinese Medicine

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized primarily by progressive cognitive impairment. Growing evidence suggests that gut–brain communication mediated by the gut microbiota and microbiota-related metabolic signals is closely associated with AD pathology. AD-related microbial alterations extend beyond changes in community composition and involve remodeling of microbial functions and host–microbiota co-metabolic networks. Microbiota-related signals, including short-chain fatty acids (SCFAs), bile acids, tryptophan-derived metabolites, trimethylamine N-oxide (TMAO), and lipopolysaccharide (LPS), may contribute to disease progression by affecting barrier homeostasis, immune and inflammatory responses, oxidative stress, and Aβ/tau proteostasis. Traditional Chinese medicine (TCM) formulas, single-herb Chinese medicines, and TCM-derived bioactive substances may simultaneously modulate microbial composition, metabolic functions, and multiple host pathological processes, thereby exhibiting multi-module and multi-node regulatory effects. This review summarizes AD-associated alterations in gut microbial metabolism and their potential pathological roles, with particular emphasis on how TCM and TCM-derived bioactive substances modulate SCFA metabolism, tryptophan and other aromatic amino acid metabolism, TMAO/LPS-related signaling, and bile acid and lipid metabolic networks, while also discussing current limitations in causal inference and clinical translation. On this basis, we propose a continuous functional validation framework linking “TCM and TCM-derived bioactive substances–microbial functions–key metabolites–host targets–AD pathological phenotypes.” Such a framework may help clarify the mechanisms by which TCM modulates host–microbiota co-metabolic networks in AD and provide a stronger basis for the clinical translation of TCM-based interventions.