Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis

Chen, Zuojia; Luo, Jialie; Li, Jian; Kim, Girak; Stewart, Andy; Urban, Joseph F.; Huang, Yao‐Zeng; Chen, Shan; Wu, Ling−Gang; Chesler, Alexander T.; Trinchieri, Giorgio; Li, Wei; Wu, Chuan

doi:10.1016/j.immuni.2020.10.014

Cited by 79 publications

(81 citation statements)

References 67 publications

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“…IE damage at the syncytial tunnels caused by the whipworm larvae either mechanically through tunnelling or chemically as induced by secretory/excretory products, potentially results in release of damage-associated molecular patterns (DAMPs) and alarmins by infected IECs, which have been suggested to initiate innate immune responses to the worm 13, 14, 37 . The production of the alarmins IL-25 38, 39 , IL-33 40, 41 and TSLP 42, 43 implicated in the induction of type 2 responses to Trichuris and other parasitic worms 37 was either not detected or did not significantly increase in our single cell or bulk transcriptomics data over the first 72 hours of infection (Supplementary Fig. 10 and 11).…”

Section: Discussionmentioning

confidence: 88%

Defining the early stages of intestinal colonisation by whipworms

Duque-Correa

Goulding

Cormie

et al. 2020

Preprint

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Hundreds of millions of people are infected with whipworms (Trichuris trichiura), large metazoan parasites that live in the caecum and proximal colon. Whipworms inhabit distinct multi-intracellular epithelial burrows that have been described as syncytial tunnels. However, the interactions between first-stage (L1) larvae and the host epithelia that determine parasite invasion and establishment in the syncytium remain unclear. In vivo experiments investigating these events have been severely hampered by the limited in situ accessibility to intracellular infective larvae at the bottom of the crypts of Lieberkuhn, and the lack of genetic tools such as fluorescent organisms that are readily available for other pathogens but not parasitic nematodes. Moreover, cell lines, which do not mimic the complexity of the intestinal epithelium, have been unsuccessful in supporting infection by whipworm larvae. Here, we show that caecaloids grown in an open crypt-like conformation recapitulate the caecal epithelium. Using this system, we establish in vitro infections with T. muris L1 larvae for the first-time, and provide clear evidence that syncytial tunnels are formed at this early stage. We show that larval whipworms are completely intracellular but woven through multiple cells. Using the caecaloids, we are able to visualise the pathways taken by the larvae as they burrow through the epithelial cells. We also demonstrate that larvae degrade the mucus layers overlaying the epithelium, enabling them to access the cells below. We show that early syncytial tunnels are composed of enterocytes and goblet cells that are alive and actively interacting with the larvae during the first 24 h of the infection. Progression of infection results in damage to host cells and by 72 h post-infection, we show that desmosomes of cells from infected epithelium widen and some host cells appear to become liquified. Collectively, our work unravels processes mediating the intestinal epithelium invasion by whipworms and reveals new specific interactions between the host and the parasite that allow the whipworm to establish on its multi-intracellular niche. Our study demonstrates that caecaloids can be used as a relevant in vitro model to investigate the infection biology of T. muris during the early colonisation of its host.

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Section: Discussionmentioning

confidence: 88%

Defining the early stages of intestinal colonisation by whipworms

Duque-Correa

Goulding

Cormie

et al. 2020

Preprint

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“…It is well known that 5-HT, as a metabolite of tryptophan, is a hormone and excitatory neurotransmitter. It not only promotes intestinal peristalsis [48,49], but also plays an essential role in depression, autism, neurodegeneration, and other diseases [50]. Many studies have shown that 5-HT plays a regulatory role by regulating the hippocampal nervous system.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus Probio-M9 Improves the Quality of Life in Stressed Adults by Gut Microbiota

Zheng

Zhang

et al. 2021

Foods

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To evaluate the effect of the probiotic, Lactobacillus rhamnosus Probio-M9 (Probio-M9), on the quality of life in stressed adults. Methods: Twelve postgraduate student volunteers were recruited. Six volunteers received oral Probio-M9 for 21 days, while the remaining six received a placebo instead. Fecal samples were collected from the volunteers before and after the intervention. Metagenomic sequencing, nontargeted metabonomics, and quality-of-life follow-up questionnaires were used to evaluate the impact of Probio-M9 consumption on the gut microbiota and life quality of the volunteers. Results: Probio-M9 improved the psychological and physiological quality-of-life symptoms significantly in stressed adults (p < 0.05). The probiotic intervention was beneficial in increasing and maintaining the diversity of gut microbiota. The abundance of Barnesiella and Akkermansia increased in the probiotics group. The feature metabolites of pyridoxamine, dopamine, and 5-hydroxytryptamine (5-HT) were positively correlated with Barnesiella and Akkermansia levels, which might be why the mental state of the volunteers in the probiotic group improved after taking Probio-M9. Conclusions: We identified that oral Probio-M9 can regulate the stability of gut microbiota and affect the related beneficial metabolites, thereby affecting the quality of life (QoL) of stressed adults. Probio-M9 might improve the psychological and physiological quality of life in stressed adults via the gut-brain axis pathway. The causal relationship should be further explored in future studies.

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“…For example, the alarmin cytokine IL-33, which is released upon epithelial cell damage, promotes the production of serotonin by enteroendocrine cells. IL-33-mediated serotonin release activated enteric neurons, which subsequently promoted gut motility [117]. Interestingly, stimulation of Group 2 innate lymphoid cells (ILC2s) by IL-33 treatment or following Nippostrongylus brasiliensis infection resulted in the upregulation of the transcript for tryptophan hydroxylase 1 (Tph1), the rate-limiting enzyme in serotonin biosynthesis [118].…”

Section: Immunological Cross Talkmentioning

confidence: 99%

The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives

Günther

Rothhammer

Karow

et al. 2021

IJMS

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The gut–brain axis is a bidirectional communication system driven by neural, hormonal, metabolic, immunological, and microbial signals. Signaling events from the gut can modulate brain function and recent evidence suggests that the gut–brain axis may play a pivotal role in linking gastrointestinal and neurological diseases. Accordingly, accumulating evidence has suggested a link between inflammatory bowel diseases (IBDs) and neurodegenerative, as well as neuroinflammatory diseases. In this context, clinical, epidemiological and experimental data have demonstrated that IBD predisposes a person to pathologies of the central nervous system (CNS). Likewise, a number of neurological disorders are associated with changes in the intestinal environment, which are indicative for disease-mediated gut–brain inter-organ communication. Although this axis was identified more than 20 years ago, the sequence of events and underlying molecular mechanisms are poorly defined. The emergence of precision medicine has uncovered the need to take into account non-intestinal symptoms in the context of IBD that could offer the opportunity to tailor therapies to individual patients. The aim of this review is to highlight recent findings supporting the clinical and biological link between the gut and brain, as well as its clinical significance for IBD as well as neurodegeneration and neuroinflammation. Finally, we focus on novel human-specific preclinical models that will help uncover disease mechanisms to better understand and modulate the function of this complex system.

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Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis

Cited by 79 publications

References 67 publications

Defining the early stages of intestinal colonisation by whipworms

Defining the early stages of intestinal colonisation by whipworms

Lactobacillus rhamnosus Probio-M9 Improves the Quality of Life in Stressed Adults by Gut Microbiota

The Gut-Brain Axis in Inflammatory Bowel Disease—Current and Future Perspectives

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