Nature. Intestinal flora promotes the excitability of intestinal neural networks to maintain intestinal physiological function.

It is very important to maintain health that XueYue nervous system regulates visceral function.intestinal peristalsis is very important for digestive system physiological function and host defense.the enteric nervous system (ENS) is an internal neural network that regulates the gastrointestinal tract. It regulates all aspects of intestinal physiological functions, including intestinal peristalsis [1].there are many factors regulating intestinal physiological function, including host specific genetic factors, intestinal microorganisms and diet.the changes of intestinal microflora are often accompanied by the occurrence of intestinal diseases.some studies have found that the removal of intestinal microorganisms can reduce the excitability of intestinal neurons, resulting in intestinal motility disorder and decreased peristalsis.however, some studies have shown that the excitability of intestinal neurons in adult sterile mice will be restored, and the phenomenon of intestinal motility disorder will be reduced.this also indicates that there is a molecular mechanism for intestinal neural network to monitor intestinal function and regulate neuronal excitability.although great progress has been made in the regulation of intestinal physiological function by diet and intestinal flora through the intestinal nervous system, the molecular mechanism of the relationship between intestinal nervous system and intestinal peristalsis regulated by intestinal microbial environment is still unclear.on February 6, 2020, Vassilis pachnis and Brigitta Stockinger research group of Francis Crick Institute in London, UK and Andrew J. MacPherson of Bern University in Switzerland jointly published an article entitled "nervous programming by microbiota regulations internal physiology" in nature.the authors found that the transcription factor aryl hydrocarbon receptor (AHR) as a biosensor of intestinal neural network can sense the microbial environment in intestinal cavity and induce expression, and participate in maintaining the excitability of intestinal neurons and regulating intestinal physiological functions.the authors first explored the up-regulated genes in intestinal neurons of mice in response to microorganisms.the authors believe that the current methods of intestinal tissue dissociation and ENS isolation will lead to cell damage and non-specific transcriptome changes. Therefore, we have developed a new method: labeling neurons with AAV, and then flow cytometry to isolate the nuclear RNA of intestinal neurons in different microbial States and different intestinal segments, and perform nrna SEQ.in order to reduce the complex environmental factors caused by diet and feeding, the authors carried out the above-mentioned methods in sterile mice, mice from the Francis Crick Institute and the University of Bern in Switzerland.comparing the three kinds of mice, it was found that 254 genes in colon neurons of SPF mice were up-regulated, and the most obvious changes were mainly in neuron differentiation and function related genes.comparing gene expression in small intestine and colon neurons of sterile mice by nrna SEQ, we found that 122 genes were up-regulated in colon neurons.comparing the nrna of colon neurons in sterile and SPF mice, we found that 25 genes were up-regulated in colon neurons of SPF mice. after removing the genes contained in the above 122 gene set, the remaining genes with increased expression were associated with intestinal microbial colonization, including AHR, dand5 and prr5. the authors focus on the AhR molecule. the transcriptional activity of AHR encoded transcription factors is regulated by microorganisms, diet and endogenous metabolites (AHR ligands), and act as biosensors in intestinal epithelial and immune cell homeostasis [2]. in order to explore the existence of intestinal flora AHR neural output axis, the authors conducted a series of experiments. the authors first found that AhR was mainly expressed in muscle layer neurons, and the expression of AHR in intestinal neurons was related to microbial load. The expression of AHR in colon of sterile mice and antibiotic treated mice decreased, and the expression of AHR increased after the restoration of colonization of microbial colonies. in order to determine the target and effector genes of AHR signal, the authors compared the transcriptome data of control group and mice treated with 3-methylcholanthrene 3mc. among the 30 genes with the highest up regulation level, ahrr and CYP1A1 are classic target genes of AHR signal. after the p-value standard was relaxed to P & lt; 0.06, the authors found that the gene kcnj12 was also in the 30 gene clusters with the most obvious changes, and there was a correlation between AHR and kcnj12 expression. the authors used AAV (AAV9 CaMKII CRE to ahrfl / FL; rosa26eyfp) to construct intestinal neuron specific AHR knockout mice, and found that the expression of kcnj12 in colon neurons decreased. experiments showed that AhR regulated by microbial expression in colonic neurons could activate the expression of AHR target genes and promote the excitability of colon neurons. the authors further explored whether AHR signals in colonic neurons regulate intestinal motility. the authors used the colon in vitro mapping to record the colonic migration, and confirmed that AhR activity can control the physiological output of the colonic neural circuit. CYP1A1 mediated the clearance of natural AHR ligands. the phenotype of CYP1A1 in colon neuron specific overexpression mice was similar to that in AHR specific knockout mice, and intestinal motility was impaired. the AhR expression and intestinal motility of wild type mice decreased after antibiotic treatment. these results indicate that AhR signal in colon neurons regulates the motor output of enteric nerve circuit. in general, the authors found that the AhR signal in intestinal neurons is an important regulatory node, which combines the intestinal microbial environment with the physiological output of the intestinal neural network, so as to maintain the intestinal physiological function. in addition to the function of AHR, AhR also regulates the barrier function of intestinal epithelial cells and mucosal immune system. AHR activity is integrated into maintaining intestinal homeostasis and host defense function by transmitting environmental triggers in a variety of cell types. link: related reading: cell point of view of "treasure edition" | it's time to put the microbiome research back on track. Rolig, A. S. et al. The internal nervous system promotes internal health by constraining microbiota composition. PLoS Biol. 15, e2000689 (2017). 2, schiering, C. et al. Feedback control of AHR signalling regulates intestinal immunity. Nature 542, 242–245 (2017).