Vasoactive Intestinal Polypeptide Plays a Key Role in the Microbial-Neuroimmune Control of Intestinal Motility

被引：15

作者：

Bai, Xiaopeng ^{[1
,2
]}

De Palma, Giada ^{[1
]}

Boschetti, Elisa ^{[3
]}

Nishiharo, Yuichiro ^{[1
]}

Lu, Jun ^{[1
]}

Shimbori, Chiko ^{[1
]}

Costanzini, Anna ^{[4
]}

Saqib, Zarwa ^{[1
]}

Kraimi, Narjis ^{[1
]}

Sidani, Sacha ^{[1
]}

Hapfelmeier, Siegfried ^{[5
]}

Macpherson, Andrew J. ^{[6
]}

Verdu, Elena F. ^{[1
]}

De Giorgio, Roberto ^{[7
]}

Collins, Stephen M. ^{[1
]}

Bercik, Premysl ^{[1
]}

机构：

[1] McMaster Univ, Farncombe Family Digest Hlth Res Inst, Dept Med, HSC 3N9, Hamilton, ON, Canada

[2] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka, Japan

[3] Univ Bologna, Dept Biomed & NeuroMotor Sci, Bologna, Italy

[4] IRCCS Azienda Osped Univ Bologna, Bologna, Italy

[5] Univ Bern, Inst Infect Dis, Bern, Switzerland

[6] Univ Hosp Bern, Dept Biomed Res, Bern, Switzerland

[7] Univ Ferrara, Dept Translat Med, Ferrara, Italy

来源：

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2024年 / 17卷 / 03期

基金：

加拿大健康研究院;

关键词：

Gastrointestinal Motility; Microbiota; Enteric Ner- vous System; Vasoactive Intestinal Polypeptide; FTY720; FINGOLIMOD; GASTROINTESTINAL MOTILITY; ENTERIC GLIA; RECEPTOR; PEPTIDE; MODEL; MECHANISM; NEURONS; COLONIZATION; DYSFUNCTION;

D O I：

10.1016/j.jcmgh.2023.11.012

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

We have identified a novel neuroimmune mechanism by which gut microbiota regulates intestinal motility that can lead to development of new treatments, including microbial therapeutics, targeting small intestinal VIP to treat chronic constipation and diarrhea. BACKGROUND & AIMS: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. METHODS: Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot. RESULTS: Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudoobstruction compared with control subjects. CONCLUSIONS: Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders. (Cell Mol Gastroenterol Hepatol 2024;17:383-398; https://doi.org/ 10.1016/j.jcmgh.2023.11.012)

引用

页码：383 / 398

页数：16

共 60 条

[1] Regionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape [J].

Agace, William W. ;

McCoy, Kathy D. .

IMMUNITY, 2017, 46 (04) :532-548

[2] Gut Microbial Products Regulate Murine Gastrointestinal Motility via Toll-Like Receptor 4 Signaling [J].

Anitha, Mallappa ;

Vijay-Kumar, Matam ;

Sitaraman, Shanthi V. ;

Gewirtz, Andrew T. ;

Srinivasan, Shanthi .

GASTROENTEROLOGY, 2012, 143 (04) :1006-+

[3] Toll-like Receptors 3, 4, and 7 Are Expressed in the Enteric Nervous System and Dorsal Root Ganglia [J].

Barajon, Isabella ;

Serrao, Graziano ;

Arnaboldi, Francesca ;

Opizzi, Emanuela ;

Ripamonti, Gerlomina ;

Balsari, Andrea ;

Rumio, Cristiano .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2009, 57 (11) :1013-1023

[4] Generation of Multimillion-Sequence 16S rRNA Gene Libraries from Complex Microbial Communities by Assembling Paired-End Illumina Reads [J].

Bartram, Andrea K. ;

Lynch, Michael D. J. ;

Stearns, Jennifer C. ;

Moreno-Hagelsieb, Gabriel ;

Neufeld, Josh D. .

APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2011, 77 (11) :3846-3852

[5] Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction [J].

Bercík, P ;

Wang, L ;

Verdü, EF ;

Mao, YK ;

Blennerhassett, P ;

Khan, WI ;

Kean, I ;

Tougas, G ;

Collins, SM .

GASTROENTEROLOGY, 2004, 127 (01) :179-187

[6] Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection [J].

Bercík, P ;

De Giorgio, R ;

Blennerhassett, P ;

Verdú, EF ;

Barbara, G ;

Collins, SM .

GASTROENTEROLOGY, 2002, 123 (04) :1205-1215

[7] The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice [J].

Bercik, Premysl ;

Denou, Emmanuel ;

Collins, Josh ;

Jackson, Wendy ;

Lu, Jun ;

Jury, Jennifer ;

Deng, Yikang ;

Blennerhassett, Patricia ;

Macri, Joseph ;

McCoy, Kathy D. ;

Verdu, Elena F. ;

Collins, Stephen M. .

GASTROENTEROLOGY, 2011, 141 (02) :599-U701

[8] Gastrointestinal motility in the neonate [J].

Berseth, CL .

CLINICS IN PERINATOLOGY, 1996, 23 (02) :179-&

[9] Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2 [J].

Bolyen, Evan ;

Rideout, Jai Ram ;

Dillon, Matthew R. ;

Bokulich, NicholasA. ;

Abnet, Christian C. ;

Al-Ghalith, Gabriel A. ;

Alexander, Harriet ;

Alm, Eric J. ;

Arumugam, Manimozhiyan ;

Asnicar, Francesco ;

Bai, Yang ;

Bisanz, Jordan E. ;

Bittinger, Kyle ;

Brejnrod, Asker ;

Brislawn, Colin J. ;

Brown, C. Titus ;

Callahan, Benjamin J. ;

Caraballo-Rodriguez, Andres Mauricio ;

Chase, John ;

Cope, Emily K. ;

Da Silva, Ricardo ;

Diener, Christian ;

Dorrestein, Pieter C. ;

Douglas, Gavin M. ;

Durall, Daniel M. ;

Duvallet, Claire ;

Edwardson, Christian F. ;

Ernst, Madeleine ;

Estaki, Mehrbod ;

Fouquier, Jennifer ;

Gauglitz, Julia M. ;

Gibbons, Sean M. ;

Gibson, Deanna L. ;

Gonzalez, Antonio ;

Gorlick, Kestrel ;

Guo, Jiarong ;

Hillmann, Benjamin ;

Holmes, Susan ;

Holste, Hannes ;

Huttenhower, Curtis ;

Huttley, Gavin A. ;

Janssen, Stefan ;

Jarmusch, Alan K. ;

Jiang, Lingjing ;

Kaehler, Benjamin D. ;

Bin Kang, Kyo ;

Keefe, Christopher R. ;

Keim, Paul ;

Kelley, Scott T. ;

Knights, Dan .

NATURE BIOTECHNOLOGY, 2019, 37 (08) :852-857

[10]

Callahan BJ, 2016, NAT METHODS, V13, P581, DOI [10.1038/nmeth.3869, 10.1038/NMETH.3869]

← 1 2 3 4 5 6 →