Akkermansia muciniphila and its outer membrane protein Amuc_1100 prophylactically attenuate 5-fluorouracil-induced intestinal mucositis

Chen, Shoujun; Qian, Kaiyue; Zhang, Guanghui; Zhang, Min

doi:10.1016/j.bbrc.2022.04.135

Cited by 16 publications

(2 citation statements)

References 29 publications

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“…Dysbiosis within the gut microbiota can lead to various adverse effects, such as diarrhea and indigestion, and is associated with inflammatory bowel diseases, such as ulcerative colitis or Crohn’s disease [ 4 , 43 ]. Interestingly, our sequencing data revealed that 5-FU disrupted the overall structure and abundance of the gut microbiota and altered the relative abundance of specific bacterial genera known to inhabit the intestine [ 11 , 12 , 21 ]. The results of α-diversity analysis indicated that high-dose CP-A decreased the richness and diversity of the microbiota.…”

Section: Discussionmentioning

confidence: 99%

“…Once the intestinal barrier is breached, an increase in intestinal epithelium permeability permits endotoxins and macromolecules to enter the cells freely, causing the release of IL-6, IL-8, TNF-α and IFN-γ, which will aggravate the inflammatory response [ 18 ]. Moreover, the destruction of the intestinal mucosal barrier is accompanied by disturbances in the intestinal microbiota [ 9 , 21 ]. Therefore, the inhibition of TNF-α and IFN-γ overexpression and the regulation of the ERK/MLCK/MLC2 pathway protect the intestinal mucosal barrier and reduce inflammation.…”

Section: Introductionmentioning

confidence: 99%

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An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota

Zhou,

Li,

Wang

et al. 2024

Pharmaceuticals

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Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Codonopsis pilosula-derived CP-A (an inulin-type fructan) is an edible Chinese medicine with anti-inflammatory and gastrointestinal protective effects, which may be useful for treating IM. Here, we explored CP-A’s role in ameliorating IM induced by 5-fluorouracil (5-FU) and investigated the underlying mechanism using in vitro experiments and rat models. Western blotting, immunohistochemistry (IHC), and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs), and 16S rRNA amplicon sequencing was employed for cecum content analysis. The results indicated that CP-A restored body weight and food intake and reversed histopathological changes in IM rats. Further, abnormal MLCK activation induced by 5-FU was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. Moreover, CP-A intervention regulated the intestinal microbiota community structure, increasing the abundance of Lactobacillus and decreasing the abundance of Shigella. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier, and regulating the intestinal microbial community. This study highlights CP-A’s therapeutic potential in IM treatment and provides insights for future research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota

Zhou,

Li,

Wang

et al. 2024

Pharmaceuticals

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Akkermansia muciniphilaisolated from forest musk deer ameliorates diarrhea in mice via modification of gut microbiota

Deng,

Wang,

Liu

et al. 2024

Anim Models and Exp Med

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BackgroundThe forest musk deer, a rare fauna species found in China, is famous for its musk secretion which is used in selected Traditional Chinese medicines. However, over‐hunting has led to musk deer becoming an endangered species, and their survival is also greatly challenged by various high incidence and high mortality respiratory and intestinal diseases such as septic pneumonia and enteritis. Accumulating evidence has demonstrated that Akkermannia muciniphila (AKK) is a promising probiotic, and we wondered whether AKK could be used as a food additive in animal breeding programmes to help prevent intestinal diseases.MethodsWe isolated one AKK strain from musk deer feces (AKK‐D) using an improved enrichment medium combined with real‐time PCR. After confirmation by 16S rRNA gene sequencing, a series of in vitro tests was conducted to evaluate the probiotic effects of AKK‐D by assessing its reproductive capability, simulated gastrointestinal fluid tolerance, acid and bile salt resistance, self‐aggregation ability, hydrophobicity, antibiotic sensitivity, hemolysis, harmful metabolite production, biofilm formation ability, and bacterial adhesion to gastrointestinal mucosa.ResultsThe AKK‐D strain has a probiotic function similar to that of the standard strain in humans (AKK‐H). An in vivo study found that AKK‐D significantly ameliorated symptoms in the enterotoxigenic Escherichia coli (ETEC)‐induced murine diarrhea model. AKK‐D improved organ damage, inhibited inflammatory responses, and improved intestinal barrier permeability. Additionally, AKK‐D promoted the reconstitution and maintenance of the homeostasis of gut microflora, as indicated by the fact that AKK‐D‐treated mice showed a decrease in Bacteroidetes and an increase in the proportion of other beneficial bacteria like Muribaculaceae, Muribaculum, and unclassified f_Lachnospiaceae compared with the diarrhea model mice.ConclusionTaken together, our data show that this novel AKK‐D strain might be a potential probiotic for use in musk deer breeding, although further extensive systematic research is still needed.

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Evaluation of the Treatment with Akkermansia muciniphila BAA-835 of Chemotherapy-induced Mucositis in Mice

Souza

Miranda

Quintanilha

et al. 2023

Probiotics & Antimicro. Prot.

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Akkermansia muciniphila and its outer membrane protein Amuc_1100 prophylactically attenuate 5-fluorouracil-induced intestinal mucositis

Cited by 16 publications

References 29 publications

An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota

An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota

Akkermansia muciniphilaisolated from forest musk deer ameliorates diarrhea in mice via modification of gut microbiota

Evaluation of the Treatment with Akkermansia muciniphila BAA-835 of Chemotherapy-induced Mucositis in Mice

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