The outer membrane protein Amuc_1100 of Akkermansia muciniphila promotes intestinal 5-HT biosynthesis and extracellular availability through TLR2 signalling.
Junchao WangWenjuan XuRongjuan WangRongrong ChengZhengquan TangMin ZhangPublished in: Food & function (2021)
Akkermansia muciniphila is a probiotic inhabiting host intestinal mucus layers and displays evident easing or therapeutic effects on host enteritis and metabolic disorders such as obesity and diabetes. The outer membrane protein Amuc_1100 of A. muciniphila is likely to play a crucial role during the interaction with the host. 5-HT is a neurotransmitter and a key signal molecule regulating the gastrointestinal tract functions and other organs, which is involved in diverse physiological and pathological processes. This study demonstrated that Amuc_1100 could promote the expression of the 5-HT synthesis rate-limiting enzyme Tph1 in RIN-14B cells and reduce the expression of the serotonin reuptake transporter (SERT) in Caco-2 cells through direct interaction with TLR2, thereby improving 5-HT biosynthesis and extracellular availability. Using antibiotic-treated mice as animal models, we found that after gavage with A. muciniphila or Amuc_1100, Tph1 expression increased and SERT expression decreased in colon tissues. The 5-HT concentrations in colon tissues and blood were markedly elevated simultaneously. We also found that A. muciniphila or Amuc_1100 improved the gastrointestinal motility function and restored gut microbiota abundance and species diversity in antibiotic-treated mice. These results suggest that A. muciniphila can regulate the host intestinal 5-HT system via its outer membrane protein Amuc_1100 and TLR2. This mechanism represented an important approach through which A. muciniphila interacts with the host and further influences 5-HT-related physiological functions. These results advance the understanding of interplay mechanisms between the gut microbiota and the host, which could be the basis for new intervention strategies for related diseases.
Keyphrases
- poor prognosis
- binding protein
- toll like receptor
- type diabetes
- immune response
- inflammatory response
- randomized controlled trial
- high fat diet induced
- metabolic syndrome
- gene expression
- insulin resistance
- cardiovascular disease
- long non coding rna
- cystic fibrosis
- cell proliferation
- newly diagnosed
- cell death
- body mass index
- drug induced
- nuclear factor
- physical activity
- signaling pathway
- staphylococcus aureus
- escherichia coli
- cell wall
- adipose tissue
- genetic diversity
- bacillus subtilis
- lactic acid