The gut as a sensory organ

Furness, John B.; Rivera, Leni R.; Cho, Hyun Jung; Bravo, David; Callaghan, Brid

doi:10.1038/nrgastro.2013.180

Cited by 399 publications

(378 citation statements)

References 162 publications

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“…Enteroendocrine cells (EECs) are key sensors of nutrients and microbial metabolites 14,25 that secrete diverse hormones and function as metabolic signal transduction units 26 . EECs have been reported to comprise 8 distinct sub-classes, such that cells expressing Sct, Cck, Gcg or GIP are traditionally termed S, I, L and K cells 14 .…”

Section: Resultsmentioning

confidence: 99%

A single-cell survey of the small intestinal epithelium

Haber

Biton

Rogel

et al. 2017

Nature

1,263

108

1,516

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Intestinal epithelial cells (IECs) absorb nutrients, respond to microbes, provide barrier function and help coordinate immune responses. We profiled 53,193 individual epithelial cells from mouse small intestine and organoids, and characterized novel subtypes and their gene signatures. We showed unexpected diversity of hormone-secreting enteroendocrine cells and constructed their novel taxonomy. We distinguished between two tuft cell subtypes, one of which expresses the epithelial cytokine TSLP and CD45 (Ptprc), the pan-immune marker not previously associated with non-hematopoietic cells. We also characterized how cell-intrinsic states and cell proportions respond to bacterial and helminth infections. Salmonella infection caused an increase in Paneth cells and enterocytes abundance, and broad activation of an antimicrobial program. In contrast, Heligmosomoides polygyrus caused an expansion of goblet and tuft cell populations. Our survey highlights new markers and programs, associates sensory molecules to cell types, and uncovers principles of gut homeostasis and response to pathogens.

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Section: Resultsmentioning

confidence: 99%

A single-cell survey of the small intestinal epithelium

Haber

Biton

Rogel

et al. 2017

Nature

1,263

108

1,516

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“…Bacterial by-products that come in contact with the gut epithelium stimulate the production of several neuropeptides including peptide YY, neuropeptide Y, cholecystokinin, glucagon-like peptide-1,2, and substance P and oxytocin (Furness et al, 2013). Following secretion, neuropeptides diffuse throughout the lamina propria, which is occupied by a variety of immune cells, until they reach the blood stream, stimulate sensory neurons or act on the vagus nerve (Cummings and Overduin, 2007;Okano-Matsumoto et al, 2011).…”

Section: Microbiota and Humoral Responsesmentioning

confidence: 99%

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Dinan

Cryan

2016

Neuropsychopharmacol

183

110

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There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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“…This axis starts with the intestinal tract, which continuously monitors and responds to the composition of its content to optimize assimilation of substrates and competitive exclusion of pathogens [28]. Microbial by-products such as short-chain fatty acids (SCFAs) and chemotactic peptides bind to receptors expressed on enteroendocrine cells (EECs) to facilitate secretion of a variety of metabolically related peptides involved in food intake, lipid storage, energy homeostasis, neurotransmission and behaviour [26,29,30].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the gut microbiome–brain axis across the lifespan

Jašarević

Morrison

Bale

2016

Phil. Trans. R. Soc. B

216

142

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In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome–brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan.

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The gut as a sensory organ

Cited by 399 publications

References 162 publications

A single-cell survey of the small intestinal epithelium

A single-cell survey of the small intestinal epithelium

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Sex differences in the gut microbiome–brain axis across the lifespan

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