Bacterial Signaling to the Nervous System through Toxins and Metabolites

Yang, Nicole J.; Chiu, Isaac M.

doi:10.1016/j.jmb.2016.12.023

Cited by 121 publications

(95 citation statements)

References 172 publications

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“…The intestine not 43 only plays a role in nutrient acquisition, but also transmits signals conveying nutrient 44 status to multiple tissues including the nervous system (6)(7)(8)(9)(10). The importance of gut-to-45 brain signaling in the regulation of both developmental and behavioral traits has now 46 been demonstrated in several systems, and a subset of the underlying biochemical 47 pathways has been identified (11)(12)(13)(14)(15)(16)(17). However, how nutrient status is assessed and 48 integrated with other cues to modulate development and behavior remains to be fully 49 described.…”

Section: Introduction 37mentioning

confidence: 99%

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

O’Donnell

Chao

Kammenga

et al. 2017

Preprint

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1Animals integrate external cues with information about internal conditions such as 2 metabolic state to execute the appropriate behavioral and developmental decisions. 3Information about food quality and quantity is assessed by the intestine and transmitted to 4 modulate neuronal functions via mechanisms that are not fully understood. The 5 conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in 6 response to cellular stressors and growth factors. Here we show that TORC2 coordinates 7 larval development and adult behaviors in response to environmental cues and feeding 8 state in the bacterivorous nematode C. elegans. During development, pheromone, 9 bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 10 insulin-like peptide in sensory neurons to promote a binary decision between 11 reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 12 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which 13 together reflect bacterial-diet dependent feeding status, thus providing a mechanism for 14 integration of food signals with external cues in the regulation of neuroendocrine gene 15 expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated 16 foraging behaviors via the PDFR-1 neuropeptide receptor. We also demonstrate that 17 genetic variation affects food-dependent larval and adult phenotypes, and identify 18 quantitative trait loci (QTL) associated with these traits. Together, these results suggest 19 that TORC2 acts as a hub for communication of feeding state information from the gut to 20 the brain, thereby contributing to modulation of neuronal function by internal state. 21

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Section: Introduction 37mentioning

confidence: 99%

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

O’Donnell

Chao

Kammenga

et al. 2017

Preprint

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“…Commensal and pathogenic microbes can alter ENS functions by electrical signalling (Kunze et al, 2009), release of neurotoxins (Yang and Chiu, 2017) or by the release of neurotransmitters including serotonin, neurotrophic factor, acetylcholine and nitric oxide (Sobko et al, 2006;Carabotti et al, 2015). Bacterial proteases or TLR ligands can also modulate neural and glial cell functions by signalling through protease-activated receptors and TLR expressed on cells of the ENS (Brun et al, 2013;Burgueno et al, 2016).…”

Section: Effect Of the Microbiota On The Enteric Nervous Systemmentioning

confidence: 99%

Host‐microbe interaction in the gastrointestinal tract

Parker

Lawson

Vaux

et al. 2017

Environmental Microbiology

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SummaryThe gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host‐microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ‐free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ‐free models. The application of cell‐based in‐vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.

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“…Because the nervous system is a master regulator of host function, this allows microbes to influence a broad range of complex physiological processes. An improved mechanistic understanding of how bacterial molecules act on the nervous system could yield improved therapeutics for treating behavioural and neurological disorders …”

Section: Introductionmentioning

confidence: 99%

“…An improved mechanistic understanding of how bacterial molecules act on the nervous system could yield improved therapeutics for treating behavioural and neurological disorders. 16 The human gut microbiota is usually stable and resilient to transient perturbations. 17 However, microbial composition or activity of the gut can be modified by a variety of factors, including internal factors such as hormonal changes, or external factors such as diet, antibiotics and stress.…”

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confidence: 99%

Steroids, stress and the gut microbiome‐brain axis

Tetel

Vries

Melcangi

et al. 2018

J Neuroendocrinology

126

109

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It is becoming well established that the gut microbiome has a profound impact on human health and disease. In this review, we explore how steroids can influence the gut microbiota and, in turn, how the gut microbiota can influence hormone levels.Within the context of the gut microbiome-brain axis, we discuss how perturbations in the gut microbiota can alter the stress axis and behaviour. In addition, human studies on the possible role of gut microbiota in depression and anxiety are examined. Finally, we present some of the challenges and important questions that need to be addressed by future research in this exciting new area at the intersection of steroids, stress, gutbrain axis and human health. K E Y W O R D Sandrogen, microbiota, oestrogen, steroid hormones, stress | INTRODUCTIONWithin each human gastrointestinal tract, there is an exclusive combination of different communities of organisms, including bacteria, viruses, archaea, protozoa and fungi, which are collectively referred to as the gut microbiota and outnumber the total amount of human cells in the human body.1 The collection of these microorganisms, their genomes and the factors that they produce are all part of the gut microbiome. 2 Increasing evidence suggests that these microorganisms actively participate in shaping and maintaining our physiology almost as an extra organ. ranging from obesity 7 and asthma 8 to a variety of brain disorders. 3,9-14The gut microbiota helps break down food and, in doing so, produces metabolites that can directly influence the physiology of host cells, including brain cells. Moreover, immune responses to pathogenic bacteria produce cytokines and lymphokines that can affect brain physiology. 15Because the nervous system is a master regulator of host function, this allows microbes to influence a broad range of complex physiologicalprocesses. An improved mechanistic understanding of how bacterial molecules act on the nervous system could yield improved therapeutics for treating behavioural and neurological disorders. 16The human gut microbiota is usually stable and resilient to transient perturbations. 17 However, microbial composition or activity of the gut can be modified by a variety of factors, including internal factors such as hormonal changes, or external factors such as diet, antibiotics and stress. 3,18 In this review, the influence of steroids and stress on the gut microbiome-brain axis is discussed, as well as the challenges that face future research in this area. | STEROID HORMONES INFLUENCE THE GUT MICROBIOTAThere is mounting evidence that steroid hormones can affect the gut microbiota. In support of steroids influencing the gut bacterial communities, sex differences have been noted in the composition of the gut microbiota, with specific phyla, family and genera variances occurring with clear effects of gonadectomy and hormone replacement on gut bacteria in rodents. [19][20][21] In mice, the sex differences in the gut microbiota observed between males and females are decreased after castration, indicating a...

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Bacterial Signaling to the Nervous System through Toxins and Metabolites

Cited by 121 publications

References 172 publications

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

Host‐microbe interaction in the gastrointestinal tract

Steroids, stress and the gut microbiome‐brain axis

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