Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection

Zhang, Wen; Lyu, Mengze; Bessman, Nicholas J.; Xie, Zili; Arifuzzaman, Mohammad; Yano, Hiroshi; Parkhurst, Christopher N.; Chu, Coco; Zhou, Lei; Putzel, Gregory G.; Li, Tingting; Jin, Wenbing; Zhou, Jordan; Hu, Hongzhen; Tsou, Amy M.; Guo, Chun-Jun; Artis, David

doi:10.1016/j.cell.2022.09.008

Cited by 52 publications

(36 citation statements)

References 107 publications

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“…Administration of SP or CGRP reversed disease severity in nociceptordeficient, Calca-and Tac1-deficient mice, highlighting that nociceptor-derived CGRP and SP have tissue-protective properties during colitis. 2,9 These studies are in line with previous work showing that CGRP participates in mucosal immunity. Whether the immunoregulatory function of nociceptors is limited to SP and CGRP remains to be elucidated, as other neuropeptides such as VIP and galanin can be released.…”

supporting

confidence: 90%

“…Further evidence underscoring a crosstalk between the microbiome and nociceptors was provided by the observation that chemical and chemogenetic ablation of Nav1.8 + or TRPV1 + nociceptors induced microbial dysbiosis. 2,9 Yet, how nociceptors exactly alter the gut microbiome composition remains an enigma. Possibly, the reduced thickness of the mucus layer impacts on nutrient availability for the commensal bacteria, thereby causing changes in microbiome composition.…”

mentioning

confidence: 99%

“…Interestingly, Zhang et al showed that mucosal biopsies of IBD patients have a dysregulated pattern of TRPV1, suggesting that defective nociceptors could be a possible cause of microbial dysbiosis and mucus defects observed in IBD patients. 9 Conversely, increased mucus secretion is one of the clinical hallmarks of irritable bowel syndrome (IBS) patients. Notably, an increase in both number and sensitization of TRPV1 + nociceptors has been reported in gut biopsies of IBS patients.…”

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confidence: 99%

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How pain sensors make the gut weep

2023

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Nociceptors in the gut are widely known for transmitting pain signals to the spinal cord. Yang et al. now identified a novel microbiome-nociceptor-goblet cell crosstalk that protects the intestinal epithelial barrier by triggering mucus secretion.The intestinal tract is equipped with an epithelial barrier that spatially separates the microbiome and the immune system to avoid unnecessary immune activation. Moreover, the gut epithelium itself is covered by a mucus layer providing a physical barrier to the microbiome. The major building blocks of mucus are MUC2 mucins, which are secreted by the goblet cell. 1 The mechanisms modulating and controlling goblet cell function are however poorly understood. In a recent issue of Cell, Yang et al. elegantly revealed that microbial-mediated activation of Nav1.8 + nociceptors innervating the gut promoted MUC2 mucin secretion by goblet cells via a CGRP-Ramp1 axis during homeostasis and in the context of colitis. 2 Initial evidence indicating a role for host goblet cell-microbiota communication in the maintenance of the mucus layer came from studies in germ-free (GF) mice. Whereas the colonic inner mucus layer of conventionally-raised mice was impenetrable to microorganisms, that of GF mice was more permeable and thinner.

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confidence: 90%

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confidence: 99%

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confidence: 99%

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How pain sensors make the gut weep

2023

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“…Neuro-immune crosstalk has been shown to shape the inflammatory response in models of airway allergy and lung bacterial infection ( 133 – 135 ). Recently, in the context of the gut, sensory nerves were shown to mediate tissue integrity through microbiota interactions, suggesting similar systems may be in place in the lung ( 136 ). Altogether, this indicates that the nervous system represents another branch to consider in the interaction between the lung microbiota, cancer, and immunity.…”

Section: Discussionmentioning

confidence: 99%

The lung, the niche, and the microbe: Exploring the lung microbiome in cancer and immunity

2023

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The lung is a complex and unique organ system whose biology is strongly influenced by environmental exposure, oxygen abundance, connection to extrapulmonary systems via a dense capillary network, and an array of immune cells that reside in the tissue at steady state. The lung also harbors a low biomass community of commensal microorganisms that are dynamic during both health and disease with the capacity to modulate regulatory immune responses during diseases such as cancer. Lung cancer is the third most common cancer worldwide with the highest mortality rate amongst cancers due to the difficulty of an early diagnosis. This review discusses the current body of work addressing the interactions between the lung microbiota and the immune system, and how these two components of the pulmonary system are linked to lung cancer development and outcomes. Bringing in lessons from broader studies examining the effects of the gut microbiota on cancer outcomes, we highlight many challenges and gaps in this nascent field.

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“…There is also increasing evidence that the gut microbiota plays a role in acute and chronic pain via its role in the maturation, morphology, and immunologic functions of microglia, another immune cell that has been implicated in mediating pain via the release of proinflammatory cytokines [ 78 , 79 ]. It has recently been demonstrated that the disruption of TRPV1 nociception led to a significant alteration in the gut microbiota as well as a significant decreased in levels of substance P, which can have tissue-protective effects on the gastrointestinal (GI) tract [ 80 ]. It has been hypothesized this may be an underlying mechanism of inflammatory bowel disease, colitis, and other chronic inflammatory conditions of the GI tract that commonly involve pain [ 80 , 81 ].…”

Section: Neuroimmune Interactionmentioning

confidence: 99%

Microbiological and Physiological Effects of Pain

Jin

Everett

Abd‐Elsayed

2023

Curr Pain Headache Rep

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Pain is an important innate defense mechanism that can dramatically alter a person’s quality of life. Understanding the microbiological and physiological effects of pain may be important in the pursuit of novel pain interventions. The three descriptors of pain recognized by the International Association for the Study of Pain are nociceptive, neuropathic, and nociplastic pain. Our review examined the current understanding of all three pain types, focusing on the key molecules involved in the manifestation of each type as well as physiological effects. Additionally, we compared the differences in painful and painless neuropathies and discussed the neuroimmune interaction involved in the manifestation of pain.

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Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection

Cited by 52 publications

References 107 publications

How pain sensors make the gut weep

How pain sensors make the gut weep

The lung, the niche, and the microbe: Exploring the lung microbiome in cancer and immunity

Microbiological and Physiological Effects of Pain

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