A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis. As a contributing factor, microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms, and for both neuroimmune and neuroendocrine systems. Here, we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases, with an emphasis on multi-omics studies and the gut virome. The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated. Finally, we discuss the role of diet, prebiotics, probiotics, postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence

Intestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The gut microbiota interacts closely with the epithelium through myriad of actions, including immune and metabolic interactions, which translate into tight connections between microbial activity and ISC function. Given the diverse functions of the gut microbiota in affecting the metabolism of macronutrients and micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, the ISC fate. Therefore, understanding the intricate host-microbiota interaction in regulating ISC homeostasis is imperative for improving gut health. Here, we review recent advances in understanding host-microbiota immune and metabolic interactions that shape ISC function, such as the role of pattern-recognition receptors and microbial metabolites, including lactate and indole metabolites. Additionally, the diverse regulatory effects of the microbiota on dietary nutrients, including proteins, carbohydrates, vitamins, and minerals (e.g. iron and zinc), are thoroughly explored in relation to their impact on ISCs. Thus, we highlight the multifaceted mechanisms governing host-microbiota interactions in ISC homeostasis. Insights gained from this review provide strategies for the development of dietary or microbiota-based interventions to foster gut health.

Host-microbiota interaction in intestinal stem cell homeostasis.

Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN's ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/β-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells.

Synbiotic Combination between Lactobacillus paracasei VL8 and Mannan-Oligosaccharide Repairs the Intestinal Barrier in the Dextran Sulfate Sodium-Induced Colitis Model by Regulating the Intestinal Stem Cell Niche.

ABSTRACT Chitosan oligosaccharide (COS) is a new type of marine functional oligosaccharide with biological activities such as regulating intestinal microflora and improving intestinal immunity. In this study, female Drosophila melanogaster was used as a model organism to evaluate the effect of COS on intestinal injury by H2O2 induction, and its mechanism was explored through the analysis of intestinal homeostasis. The results showed that 0.25% of COS could effectively prolong the lifespan of stressed female D. melanogaster by increasing its antioxidant capacity and maintaining intestinal homeostasis, which included protecting the mechanical barrier, promoting the chemical barrier, and regulating the biological barrier by affecting its autophagy and the antioxidant signaling pathway. Additionally, the protective effect of COS on the intestinal barrier and homeostasis of D. melanogaster under oxidative stress status is directly related to its regulation of the intestinal microflora, which could decrease excessive autophagy and activate the antioxidant system to promote health. IMPORTANCE The epithelial barrier plays an important role in the organism’s health. Chitosan oligosaccharide (COS), a new potential prebiotic, exhibits excellent antioxidant capacity and anti-inflammatory effects. Our study elucidated the protective mechanisms of COS on the intestinal barrier of Drosophila melanogaster under oxidative stress, which could provide new insights into COS application in various industries, such as food, agriculture, and medicine.

Chitosan oligosaccharide improves intestinal homeostasis to achieve the protection for the epithelial barrier of female Drosophila melanogaster via regulating intestinal microflora

Colorectal cancer is a global health concern with high incidence and mortality rates. Conventional treatments like surgery, chemotherapy, and radiation therapy have limitations in improving patient survival rates. Recent research highlights the role of gut microbiota and intestinal stem cells in maintaining intestinal health and their potential therapeutic applications in colorectal cancer treatment. The interaction between gut microbiota and stem cells influences epithelial self-renewal and overall intestinal homeostasis. Novel therapeutic approaches, including immunotherapy, targeted therapy, regenerative medicine using stem cells, and modulation of gut microbiota, are being explored to improve treatment outcomes. Accordingly, this chapter provides an overview of the potential therapeutic applications of gut microbiota and intestinal stem cells in treating colorectal cancer. 

The Potential Role of Intestinal Stem Cells and Microbiota for the Treatment of Colorectal Cancer

Key regulators of intestinal stem cells: diet, microbiota, and microbial metabolites.

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Key regulators of intestinal stem cells: diet, microbiota, and microbial metabolites.