Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.

Diverse liver diseases undergo a similar pathophysiological process in which liver regeneration follows a liver injury. Given the important role of the gut-liver axis in health and diseases, the role of gut microbiota-derived signals in liver injury and regeneration has attracted much attention. It has been observed that the composition of gut microbiota dynamically changes in the process of liver regeneration after partial hepatectomy, and gut microbiota modulation by antibiotics or probiotics affects both liver injury and regeneration. Mechanically, through the portal vein, the liver is constantly exposed to gut microbial components and metabolites, which have immense effects on the immunity and metabolism of the host. Emerging data demonstrate that gut-derived lipopolysaccharide, gut microbiota-associated bile acids, and other bacterial metabolites, such as short-chain fatty acids and tryptophan metabolites, may play multifaceted roles in liver injury and regeneration. In this perspective, we provide an overview of the possible molecular mechanisms by which gut microbiota-derived signals modulate liver injury and regeneration, highlighting the potential roles of gut microbiota in the development of gut microbiota-based therapies to alleviate liver injury and promote liver regeneration.

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