OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

The correlation between intestinal flora and diseases has become a hot research topic in recent years.Since the incidence of diabetes is closely related to chronic low-grade inflammation and intestinal flora disorders,the intervention of intestinal flora imbalance has become a research focus in the prevention and treatment of diabetes mellitus.Akkermansia muciniphila(A.muciniphila) stands out among the intestinal flora as it can alleviate the diabetes-related symptoms by regulating glucagon-like peptide 1 (GLP-1) level,improving intestinal barrier function,and inhibiting chronic inflammation,which is a potential target for the prevention and treatment of diabetes.The reduction in the abundance of A.muciniphila is a marker for the early diagnosis of diabetes.The available studies have demonstrated that the administration with A.muciniphila alone can significantly attenuate inflammation and other related symptoms of diabetic patients.Moreover,A.muciniphila has good safety and can be tolerated by human body.Therefore,A.muciniphila has the potential to serve as a new species of probiotics for the treatment of diabetes.The clinical measures for treating diabetes,such as metformin,Chinese herbal medicines,and functional diet,have been confirmed to be associated with the increased abundance of A.muciniphila.Among them,Chinese herbal medicines can treat diabetes via multiple targets and pathways in a systemic manner.Studies have reported that A.muciniphila is a potential target of Chinese herbal medicines intervening in diabetes.After the administration of Chinese herbal medicines,the improvement of diabetes-related indicators was positively correlated with the abundance of A.muciniphila.The above evidence provides a new idea for the research on the interaction between Chinese herbal medicines and intestinal flora in the treatment of diabetes.Therefore,this paper reviewed the role of A.muciniphila in diabetes and the correlation between the abundance of A.muciniphila and the administration of Chinese herbal medicines,aiming to provide new measures for the prevention and treatment of diabetes.
Humans ; Diabetes Mellitus/prevention & control* ; Akkermansia ; Inflammation ; Plant Extracts

Akkermansia muciniphila, abbreviated as AKK and found in 2004, is an oval-shaped gram-negative bacterium isolated from a human feal. A. muciniphila is widely present in the intestinal tract of human. Its specialization in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells. More and more studies have shown that it can play the role of probiotics. Notably, declined levels of A. muciniphila have been observed in patients with diabetes, liver disease, cardiovascular disease, inflammatory bowel disease, neurodegenerative diseases, etc. In addition, A. muciniphila combined with traditional Chinese medicine, exhibited higher effect on regulating host functions, but the underlying mechanism was still unclear, requiring further in-depth research. Therefore, the aims of this review are to summarize the main effects of A. muciniphila on host health and its relationship with traditional Chinese medicine, summarize the main problems, and provide a reference for the further research of A. muciniphila and traditional Chinese medicine.
Akkermansia ; Humans ; Inflammatory Bowel Diseases ; Intestines ; Probiotics ; Verrucomicrobia/genetics*

Akkermansia ; Colitis ; Colorectal Neoplasms ; Humans ; Inflammatory Bowel Diseases ; Verrucomicrobia