scholarly journals Host Gut Motility and Bacterial Competition Drive Instability in a Model Intestinal Microbiota

2016 ◽  
Author(s):  
Travis J. Wiles ◽  
Matthew L. Jemielita ◽  
Ryan P. Baker ◽  
Brandon H. Schlomann ◽  
Savannah L. Logan ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Enteric Nervous System ◽  
Bacterial Species ◽  
Stochastic Perturbation ◽  
Hirschsprung Disease ◽  
Light Sheet ◽  
Mitigation Strategies ◽  
Gut Motility ◽  
Bacterial Competition

AbstractThe gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this ‘microbial organ’ for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within the vertebrate gut. We observed that the interplay between each population and the gut environment produced distinct spatiotemporal patterns. Consequently, one species dominates while the other experiences dramatic collapses that are well fit by a stochastic mathematical model. Modeling revealed that bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to mutation in the Hirschsprung disease locus ret. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities along with bacterial competition drives population dynamics within the gut. In addition, this work highlights the capacity of the enteric nervous system to affect stability of gut microbiota constituents, demonstrating that the ‘gut-brain axis’ is bidirectional. Ultimately, these findings will help inform disease mitigation strategies focused on engineering the intestinal ecosystem.

scholarly journals “Too much guts and not enough brains”: (epi)genetic mechanisms and future therapies of Hirschsprung disease — a review

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Emilie G. Jaroy ◽  
Lourdes Acosta-Jimenez ◽  
Ryo Hotta ◽  
Allan M. Goldstein ◽  
Ragnhild Emblem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Current Knowledge ◽  
Hirschsprung Disease ◽  
Gut Development ◽  
Dna And Rna ◽  
Expression Of Genes

Abstract Hirschsprung disease is a neurocristopathy, characterized by aganglionosis in the distal bowel. It is caused by failure of the enteric nervous system progenitors to migrate, proliferate, and differentiate in the gut. Development of an enteric nervous system is a tightly regulated process. Both the neural crest cells and the surrounding environment are regulated by different genes, signaling pathways, and morphogens. For this process to be successful, the timing of gene expression is crucial. Hence, alterations in expression of genes specific for the enteric nervous system may contribute to the pathogenesis of Hirschsprung’s disease. Several epigenetic mechanisms contribute to regulate gene expression, such as modifications of DNA and RNA, histone modifications, and microRNAs. Here, we review the current knowledge of epigenetic and epitranscriptomic regulation in the development of the enteric nervous system and its potential significance for the pathogenesis of Hirschsprung’s disease. We also discuss possible future therapies and how targeting epigenetic and epitranscriptomic mechanisms may open new avenues for novel treatment.

Developmental markers of ganglion cells in the enteric nervous system and their application for evaluation of Hirschsprung disease

2014 ◽  
Vol 64 (9) ◽  
pp. 432-442 ◽  
Author(s):  
Hitomi Kawai ◽  
Kaishi Satomi ◽  
Yukio Morishita ◽  
Yoshihiko Murata ◽  
Masato Sugano ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Ganglion Cells ◽  
Hirschsprung Disease

scholarly journals A309 ANTIBIOTIC DRIVEN CHANGES IN GUT MOTILITY HIGHLIGHT DIRECT MODULATION OF ENTERIC NERVOUS SYSTEM

2018 ◽  
Vol 1 (suppl_1) ◽  
pp. 536-536
Author(s):  
T N Delungahawatta ◽  
J Y Amin ◽  
A Stanisz ◽  
J Bienenstock ◽  
P Forsythe ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Gut Motility ◽  
Direct Modulation

scholarly journals Significant Association of rs2147555 Genetic Polymorphism in the EDNRB Gene with Hirschsprung Disease in Southern Chinese Children

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yi Zheng ◽  
ChaoTing Lan ◽  
Ning Wang ◽  
Xiaogang Xu ◽  
Tuqun Hu ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Significant Risk ◽  
Hirschsprung Disease ◽  
Recessive Model ◽  
Abnormal Development ◽  
Chinese Han ◽  
Southern Chinese ◽  
Ednrb Gene ◽  
Genetic And Environmental Factors

Hirschsprung disease (HSCR) is a human birth defect at the clinical setting, usually characterized by an absent enteric nervous system (ENS) from the distal bowel. The majority of HSCR cases represent a complex disorder resulting from the interaction of multiple genetic and environmental factors. Genetic events have been described to be involved in the abnormal development of the enteric nervous system. Although variants in several genes like RET and EDNRB have been suggested to contribute major risks to HSCR, very little is known about their involvement in the onset of HSCR. Here, we studied a large Chinese Han cohort consisting of 1,470 HSCR patients and 1,473 non-HSCR controls to further test whether there are more variants in EDNRB associated with HSCR. Our results provided the first evidence that rs2147555 in EDNRB confers a significant risk of HSCR in a Chinese Han population for both allelic frequencies ( P = 4.16 × 10 − 3 ; OR = 1.29 ) and genotypic frequencies assuming either a dominant or recessive model ( P = 0.011 and P = 0.027 , respectively). When different subtypes of HSCR cases were analyzed, the association remained significant ( OR = 1.33 , P = 0.003 for short-segment HSCR; OR = 1.34 , P = 0.044 for long segment HSCR).

NTF-3, a gene involved in the enteric nervous system development, as a candidate gene for Hirschsprung disease

2008 ◽  
Vol 43 (7) ◽  
pp. 1308-1311 ◽  
Author(s):  
Macarena Ruiz-Ferrer ◽  
Raquel M. Fernandez ◽  
Guillermo Antiñolo ◽  
Manuel Lopez-Alonso ◽  
Salud Borrego
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Candidate Gene ◽  
System Development ◽  
Hirschsprung Disease ◽  
Nervous System Development ◽  
Enteric Nervous System Development

scholarly journals Bioengineered intestinal muscularis complexes with long-term spontaneous and periodic contractions

2017 ◽  
Author(s):  
Qianqian Wang ◽  
Ke Wang ◽  
R. Sergio Solorzano-Vargas ◽  
Po-Yu Lin ◽  
Christopher M. Walthers ◽  
...  
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Enteric Nervous System ◽  
Interstitial Cells Of Cajal ◽  
Muscle Cells ◽  
Gut Motility ◽  
Spontaneous Contractions ◽  
Cells Of Cajal

AbstractAlthough critical for studies of gut motility and intestinal regeneration, the in vitro culture of intestinal muscularis with peristaltic function remains a significant challenge. Periodic contractions of intestinal muscularis result from the coordinated activity of smooth muscle cells (SMC), the enteric nervous system (ENS), and interstitial cells of Cajal (ICC). Reproducing this activity requires the preservation of all these cells in one system. Here we report the first serum-free culture methodology that consistently maintains spontaneous and periodic contractions of murine and human intestinal muscularis cells for months. In this system, SMC expressed the mature marker myosin heavy chain, and multipolar/dipolar ICC, uniaxonal/multipolar neurons and glial cells were present. Furthermore, drugs affecting ENS, ICC or SMC altered the contractions. Combining this method with scaffolds, contracting cell sheets were formed with organized architecture. With the addition of intestinal epithelial cells, this platform enabled at least 9 types of cells from mucosa and muscularis to coexist and function. The method constitutes a powerful tool for mechanistic studies of gut motility disorders and the regeneration of full-thickness engineered intestine.In the small intestine, the mucosa processes partially digested food and absorbs nutrients while the muscularis actuates the peristaltic flow to transport luminal content aborally. Gut motility is central to its digestive and absorptive function. The intestinal muscularis contains various types of cells: of these, smooth muscle cells, the enteric nervous system (ENS)1,2, and the pacemaker interstitial cells of Cajal (ICC)3 are three important players involved in the development of gut motility. Recent studies on intestinal tissue engineering have highlighted the importance of regenerating the functional intestinal muscularis4–9. A variety of systems derived from different cell sources, including pluripotent stem cells (PSC)4–6, embryonic stem cells (ESC)7 and primary tissue8,9, have been established to accomplish this goal and different contractile activities were developed in these systems. Notably, spontaneous contractions have been generated in culture systems that contained both ICC and smooth muscle cells4,6,10–13. In addition, electrical-induced neurogenic contractions were also successfully produced4,5,8 when ENS was introduced into culture. In one of the most recent studies, both spontaneous contractions and electrical-induced neurogenic contractions were developed in a PSC-based culture system4.

scholarly journals Fecal Supernatant from Adult with Autism Spectrum Disorder Alters Digestive Functions, Intestinal Epithelial Barrier, and Enteric Nervous System

2021 ◽  
Vol 9 (8) ◽  
pp. 1723
Author(s):  
Jacques Gonzales ◽  
Justine Marchix ◽  
Laetitia Aymeric ◽  
Catherine Le Berre-Scoul ◽  
Johanna Zoppi ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Enteric Nervous System ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Rrna Gene ◽  
Intestinal Epithelial ◽  
Microbiota Composition ◽  
Α Diversity

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders defined by impaired social interactions and communication with repetitive behaviors, activities, or interests. Gastrointestinal (GI) disturbances and gut microbiota dysbiosis are frequently associated with ASD in childhood. However, it is not known whether microbiota dysbiosis in ASD patients also occurs in adulthood. Further, the consequences of altered gut microbiota on digestive functions and the enteric nervous system (ENS) remain unexplored. Therefore, we studied, in mice, the ability offecal supernatant (FS) from adult ASD patients to induce GI dysfunctions and ENS remodeling. First, the analyses of the fecal microbiota composition in adult ASD patients indicated a reduced α-diversity and increased abundance of three bacterial 16S rRNA gene amplicon sequence variants compared to healthy controls (HC). The transfer of FS from ASD patients (FS–ASD) to mice decreased colonic barrier permeability by 29% and 58% compared to FS–HC for paracellular and transcellular permeability, respectively. These effects are associated with the reduced expression of the tight junction proteins JAM-A, ZO-2, cingulin, and proinflammatory cytokines TNFα and IL1β. In addition, the expression of glial and neuronal molecules was reduced by FS–ASD as compared to FS-HC in particular for those involved in neuronal connectivity (βIII-tubulin and synapsin decreased by 31% and 67%, respectively). Our data suggest that changes in microbiota composition in ASD may contribute to GI alterations, and in part, via ENS remodeling.

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