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ABSTRACT: Akkermansia muciniphila-derived extracellular vesicles alleviate colitis-related cognitive impairment+gut metagenome

PROVIDER: PRJNA1272734 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33853014_1.fastq.gz	Fastqsanger.gz
	SRR33853014_2.fastq.gz	Fastqsanger.gz
	SRR33853015_1.fastq.gz	Fastqsanger.gz
	SRR33853015_2.fastq.gz	Fastqsanger.gz
	SRR33853016_1.fastq.gz	Fastqsanger.gz

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Project description:Histone lysine lactylation (Klac) is a new posttranslational modification (PTM) that is installed by acetyltransferase to modulate specific immune responses1 and oncogenesis2,3. Akkermansia muciniphila (A. muciniphila) is a beneficial bacterium that blunts ulcerative colitis (UC) in a mouse model by secreting extracellular vesicles (SEVs)4. Although many histone sites are known to contain lysine lactylation, whether this modification is regulated to modulate specific biological functions by exogenous acetyltransferase or intestinal microbiota is not well understood. Here, we discovered that SEV from A. muciniphila, rather than A. muciniphila per se, has anti-Th17 (T helper 17) differentiation activity. We further screened the composition of SEV and found that Amuc_2172 is the key active component. As a GCN5-related acetyltransferase of A. muciniphila, Amuc_2172 is accessible to naïve T cells and functions as a lactylation transferase on Lys4 of histone H3. Accelerated histone H3 lactylation (H3Klac) on Lys4 competitively blocks trimethylation (H3Kme3) on Il17a loci in the process of Th17-cell differentiation. Additionally, intraperitoneal application of recombinant Amuc_2172 also inhibited Th17 and dextran sulfate sodium (DSS)-induced UC phenotypes in vivo; moreover, bioengineered Amuc_2172 showed improved colitis site delivery and higher Th17 inhibition potential compared to Amuc_2172 alone. Our study reveals not only a potential therapeutic strategy for treating colitis but also a model via which lysine lactylation is regulated by the intestinal microbiota, which may be broadly applicable to understand the crosstalk of bacteria and immunity.

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