The liver–brain–gut neural arc maintains the Treg cell niche in the gut

Teratani, Toshiaki; Mikami, Yohei; Nakamoto, Nobuhiro; Suzuki, Takahiro; Harada, Yosuke; Okabayashi, Koji; Hagihara, Yuya; Taniki, Nobuhito; Kohno, Keita; Shibata, Shinsuke; Miyamoto, Kentaro; Ishigame, Harumichi; Chu, Po–Sung; Sujino, Tomohisa; Suda, Wataru; Hattori, Masahira; Matsui, Masanao; Okada, Takaharu; Okano, Hideyuki; Inoue, M.; Yada, Toshihiko; Kitagawa, Yuko; Yoshimura, Akihiko; Tanida, Mamoru; Tsuda, Makoto; Iwasaki, Yusaku; Kanai, Takanori

doi:10.1038/s41586-020-2425-3

Cited by 162 publications

(141 citation statements)

References 73 publications

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“…Recently, the multiple-organ network that runs through the autonomic neural pathway maintaining biological homeostasis, and is involved in various pathologies (Hayakawa et al, 2017;Kamiya et al, 2019;Imai et al, 2008;Izumi et al, 2018), has garnered attention. For example, the autonomic nervous activity contributes to the suppression of hyperglycemia during liver damage by regulating pancreas β cell activity (Imai et al, 2008), to the progression of cancers (Hayakawa et al, 2017;Kamiya et al, 2019), to liver regeneration upon severe liver damage (Izumi et al, 2018) and to inflammatory bowel diseases (Teratani et al, 2020). In addition, we recently demonstrated that the autonomic nervous system contributes to liver regeneration through signal transduction from the damaged liver to activate serotonin synthesis in the small intestine through the afferent sympathetic nerves and the brain (Inoue et al, 2018;Kamimura et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

Kamimura

Owaki

et al. 2021

Disease Models &Amp; Mechanisms

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The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

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Section: Introductionmentioning

confidence: 99%

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

Kamimura

Owaki

et al. 2021

Disease Models &Amp; Mechanisms

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“…In this reflex, peripheral inflammation is sensed by vagal afferent neurons, activating a brainstem circuit that leads to decreased cytokine production via vagal afferent neuron signaling [70]. Most recently, Teratani et al reported the biological mechanism by which bacterial information from the intestinal tract is integrated in the liver and transmitted to the brain to control the production of intestinal regulatory T cells through the vagal nerve reflex [73]. Thus, several experimental approaches have been reported on autonomic innervation of immune organs and neuroimmune modulation [74].…”

Section: Gut Dysbiosis In Agidmentioning

confidence: 99%

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Nakane

Mukaino

Ihara

et al. 2020

Immunological Medicine

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Autoimmune gastrointestinal dysmotility (AGID), an idiopathic or paraneoplastic phenomenon, is a clinical form of limited autoimmune dysautonomia. The symptoms of AGID and gastrointestinal manifestations in patients with autoimmune rheumatic diseases are overlapping. Antineuronal autoantibodies are often detected in patients with AGID. Autoantibodies play a key role in GI dysmotility; however, whether they cause neuronal destruction is unknown. Hence, the connection between the presence of these autoantibodies and the specific interference in synaptic transmission in the plexus ganglia of the enteric nervous system has to be determined. The treatment options for AGID are not well-defined. However, theoretically, immunomodulatory therapies have been shown to be effective and are therefore used as the first line of treatment. Nonetheless, diverse combined immunomodulatory therapies should be considered for intractable cases of AGID. We recommend comprehensive autoimmune evaluation and cancer screening for clinical diagnosis of AGID. Univocal diagnostic criteria, treatment protocols, and outcome definitions for AGID are required for prompt diagnosis and treatment and appropriate management of immunotherapy, which will circumvent the need for surgeries and improve patient outcome. In conclusion, AGID, a disease at the interface of clinical immunology and neurogastroenterology, requires further investigations and warrants cooperation among specialists, especially clinical immunologists, gastroenterologists, and neurologists.

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“…In 1911, the Russian immunologist Metchnikoff advocated probiotics' agelessness theory that health could be enhanced and senility delayed by manipulating the intestinal microbiome with host-friendly bacteria found in yogurt because Bulgarians who consumed large amounts of yogurt had long life spans [1]. Fermentation was a prototypical example of the symbiotic relationship between humans and the gut microbiome, further forming a beneficial intestinal environment, including barrier function and immunity [2][3][4][5][6][7]. However, these symbiotic ties have gradually grown weaker since the invention of the antibiotic penicillin.…”

Section: Introductionmentioning

confidence: 99%

Bacteriotherapy for inflammatory bowel disease

2021

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The number of patients with inflammatory bowel disease is rapidly increasing in developed countries. The main cause of this increase is thought not to be genetic, but secondary to rapidly modernized environmental change. Changes in the environment have been detrimental to enteric probiotics useful for fermentation, inducing an increase in pathobionts that survive by means other than fermentation. This dysregulated microbiota composition, the so-called dysbiosis, is believed to have increased the incidence of inflammatory bowel disease. Bacteriotherapy, a treatment that prophylactically and therapeutically corrects the composition of disturbed intestinal microbiota, is a promising recent development. In fact, fecal microbiome transplantation for recurrent Clostridioides difficile infection in 2013 was a significant contribution for bacteriotherapy. In this paper, we comprehensively review bacteriotherapy in an easy-to-understand format.

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The liver–brain–gut neural arc maintains the Treg cell niche in the gut

Cited by 162 publications

References 73 publications

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

Autoimmune gastrointestinal dysmotility: the interface between clinical immunology and neurogastroenterology

Bacteriotherapy for inflammatory bowel disease

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