Collection

Gut-brain axis

It is becoming increasingly evident that bidirectional signalling exists between the gastrointestinal tract and the brain, often involving the gut microbiota. This relationship, commonly dubbed the gut–brain axis (or the microbiota–gut–brain axis), involves various afferent and efferent pathways such as the vagus nerve and the hypothalamic-pituitary-adrenal pathway to regulate aspects of homeostasis such as satiety and hunger, and inflammation. Disruption of the gut–brain axis has been shown to be involved in the pathogenesis of a diverse range of diseases, including Parkinson disease and irritable bowel syndrome. This emerging area of research is evolving quickly.

This collection brings together Research, Reviews and News from across the Nature Research journals covering key aspects of the gut–brain axis including immune, neuroendocrine and neural factors. The selected content has been published within the past 2 years in Nature Reviews Gastroenterology & Hepatology, Nature, Nature CommunicationsNature Immunology, Nature Medicine, Nature Microbiology, Nature Neuroscience, Nature Outlook, Nature Reviews Disease Primers, Nature Reviews Endocrinology, Nature Reviews Microbiology, Nature Reviews NeurologyNature Reviews Neuroscience, Nature Reviews Urology and Scientific Reports.

Articles in the core collection have been made freely available for 6 months (until 11th July 2018), thanks to support from Abbott. The collection content is editorially independent and the sole responsibility of Springer Nature.

Image credit: Laura Marshall

Core collection - FREE

  • Nature Neuroscience | Article

    In this study, the authors show that host microbiota play a key role in modulating microglia homeostasis. Germ-free mice or mice with only limited microbiota complexity displayed defects in microglial cell proportions and maturation, leading to impaired innate immune responses. The authors find that short-chain fatty acid signaling regulates these effects in vivo.

    • Daniel Erny
    • , Anna Lena Hrabě de Angelis
    • , Diego Jaitin
    • , Peter Wieghofer
    • , Ori Staszewski
    • , Eyal David
    • , Hadas Keren-Shaul
    • , Tanel Mahlakoiv
    • , Kristin Jakobshagen
    • , Thorsten Buch
    • , Vera Schwierzeck
    • , Olaf Utermöhlen
    • , Eunyoung Chun
    • , Wendy S Garrett
    • , Kathy D McCoy
    • , Andreas Diefenbach
    • , Peter Staeheli
    • , Bärbel Stecher
    • , Ido Amit
    •  &  Marco Prinz
  • Nature Medicine | Article

    Alterations in the gut microbiota affect stroke outcomes via modulation of T cells, suggesting a gut-brain axis linking commensal microbes with the CNS.

    • Corinne Benakis
    • , David Brea
    • , Silvia Caballero
    • , Giuseppe Faraco
    • , Jamie Moore
    • , Michelle Murphy
    • , Giulia Sita
    • , Gianfranco Racchumi
    • , Lilan Ling
    • , Eric G Pamer
    • , Costantino Iadecola
    •  &  Josef Anrather
  • Nature | Article

    Increased acetate production by an altered gut microbiota in rats fed a high-fat diet activates the parasympathetic nervous system, which in turn promotes increased insulin secretion, increased food intake, obesity and related changes.

    • Rachel J. Perry
    • , Liang Peng
    • , Natasha A. Barry
    • , Gary W. Cline
    • , Dongyan Zhang
    • , Rebecca L. Cardone
    • , Kitt Falk Petersen
    • , Richard G. Kibbey
    • , Andrew L. Goodman
    •  &  Gerald I. Shulman
  • Nature Reviews Gastroenterology & Hepatology | Review

    Bidirectional gut–brain communications are proving key to both gastrointestinal and neurological diseases. This Review explores the role of the mucosal immune system as gatekeeper and master regulator of these brain–gut and gut–brain communications.

    • Nick Powell
    • , Marjorie M. Walker
    •  &  Nicholas J. Talley
  • Nature Immunology | Review

    Magarian Blander and colleagues review the effects of the microbiome on innate and adaptive immunological players and how microbiota-derived bioactive molecules affect inflammation and the host response to infection, vaccination and cancer.

    • J Magarian Blander
    • , Randy S Longman
    • , Iliyan D Iliev
    • , Gregory F Sonnenberg
    •  &  David Artis

Research

  • Nature Medicine | Article

    After upregulation of AHR in astrocytes by type I interferons, commensal-microbe-derived metabolites of dietary tryptophan act on astrocytes to suppress CNS inflammation.

    • Veit Rothhammer
    • , Ivan D Mascanfroni
    • , Lukas Bunse
    • , Maisa C Takenaka
    • , Jessica E Kenison
    • , Lior Mayo
    • , Chun-Cheih Chao
    • , Bonny Patel
    • , Raymond Yan
    • , Manon Blain
    • , Jorge I Alvarez
    • , Hania Kébir
    • , Niroshana Anandasabapathy
    • , Guillermo Izquierdo
    • , Steffen Jung
    • , Nikolaus Obholzer
    • , Nathalie Pochet
    • , Clary B Clish
    • , Marco Prinz
    • , Alexandre Prat
    • , Jack Antel
    •  &  Francisco J Quintana
  • Nature Neuroscience | Brief Communication

    Recent evidence supports a functional connection between gut microbiota and the nervous system. Here the authors show that gut microbiota plays a critical role in the development of chemotherapy-induced pain. This role of the microbiota is likely mediated, in part, by Tlr4 expressed on hematopoietic cells, including macrophages.

    • Shiqian Shen
    • , Grewo Lim
    • , Zerong You
    • , Weihua Ding
    • , Peigen Huang
    • , Chongzhao Ran
    • , Jason Doheny
    • , Peter Caravan
    • , Samuel Tate
    • , Kun Hu
    • , Hyangin Kim
    • , Michael McCabe
    • , Bo Huang
    • , Zhongcong Xie
    • , Douglas Kwon
    • , Lucy Chen
    •  &  Jianren Mao
  • Nature Communications | Article

    There is growing evidence that the intestinal microbiota can affect host behaviour. Here, De Palma et al. show in mice that early-life stress (maternal separation) induces changes in host physiology that alter the gut microbiota, which then triggers anxiety-like and depression-like behaviour later in life.

    • G. De Palma
    • , P. Blennerhassett
    • , J. Lu
    • , Y. Deng
    • , A. J. Park
    • , W. Green
    • , E. Denou
    • , M. A. Silva
    • , A. Santacruz
    • , Y. Sanz
    • , M. G. Surette
    • , E. F. Verdu
    • , S. M. Collins
    •  &  P. Bercik
  • Nature Communications | Article | open

    There is concern about potential long-term effects of antibiotics on children’s health. Here Leclercq et al. show, in mice, that low doses of penicillin during late pregnancy and early life induce lasting effects on the offspring, including alterations in gut microbiota, brain cytokine levels and behaviour.

    • Sophie Leclercq
    • , Firoz M. Mian
    • , Andrew M. Stanisz
    • , Laure B. Bindels
    • , Emmanuel Cambier
    • , Hila Ben-Amram
    • , Omry Koren
    • , Paul Forsythe
    •  &  John Bienenstock
  • Nature | Article

    Lipopolysaccharide derived from gut bacteria can accelerate the formation of cerebral cavernous malformations by activating TLR4 on endothelial cells, and polymorphisms that increase expression of the genes encoding TLR4 or its co-receptor CD14 are associated with higher CCM lesion burden in humans.

    • Alan T. Tang
    • , Jaesung P. Choi
    • , Jonathan J. Kotzin
    • , Yiqing Yang
    • , Courtney C. Hong
    • , Nicholas Hobson
    • , Romuald Girard
    • , Hussein A. Zeineddine
    • , Rhonda Lightle
    • , Thomas Moore
    • , Ying Cao
    • , Robert Shenkar
    • , Mei Chen
    • , Patricia Mericko
    • , Jisheng Yang
    • , Li Li
    • , Ceylan Tanes
    • , Dmytro Kobuley
    • , Urmo Võsa
    • , Kevin J. Whitehead
    • , Dean Y. Li
    • , Lude Franke
    • , Blaine Hart
    • , Markus Schwaninger
    • , Jorge Henao-Mejia
    • , Leslie Morrison
    • , Helen Kim
    • , Issam A. Awad
    • , Xiangjian Zheng
    •  &  Mark L. Kahn
  • Nature Medicine | Article

    In humans and rodent models, commensal gut bacteria contribute to post-stroke infection. Experimental stroke in rodents causes gut barrier dysfunction and permeability, enabling translocation and dissemination of host gut microbiota.

    • Dragana Stanley
    • , Linda J Mason
    • , Kate E Mackin
    • , Yogitha N Srikhanta
    • , Dena Lyras
    • , Monica D Prakash
    • , Kulmira Nurgali
    • , Andres Venegas
    • , Michael D Hill
    • , Robert J Moore
    •  &  Connie H Y Wong

Reviews & Comment

  • Nature Reviews Neurology | Review

    Parkinson disease is defined by its motor symptoms, but onset of nonmotor symptoms, including constipation, can start much earlier. In this Review, Klingelhoefer and Reichmann present the evidence that the pathogenesis of Parkinson disease starts in the gut and is transferred to the CNS via trans-synaptic cell-to-cell transport that initiates a cascade of α-synuclein aggregation. They also consider how this process might be triggered by environmental factors, and how these earliest stages of pathogenesis might be targeted to delay or prevent disease progression.

    • Lisa Klingelhoefer
    •  &  Heinz Reichmann
  • Nature Reviews Endocrinology | Review

    Here, Patrice Cani and colleagues discuss interactions between gut microorganisms, the endocannabinoid system and host metabolism, in the context of both physiology and pathophysiology. The authors highlight the importance of gut barrier function by discussing the role of specific factors involved in intestinal permeability and their role in the gut microbiota–endocannabinoid system axis. The therapeutic potential of targeting the endocannabinoid system to treat cardiometabolic disorders and intestinal inflammation is also discussed.

    • Patrice D. Cani
    • , Hubert Plovier
    • , Matthias Van Hul
    • , Lucie Geurts
    • , Nathalie M. Delzenne
    • , Céline Druart
    •  &  Amandine Everard
  • Nature Immunology | Review

    Magarian Blander and colleagues review the effects of the microbiome on innate and adaptive immunological players and how microbiota-derived bioactive molecules affect inflammation and the host response to infection, vaccination and cancer.

    • J Magarian Blander
    • , Randy S Longman
    • , Iliyan D Iliev
    • , Gregory F Sonnenberg
    •  &  David Artis
  • Nature Reviews Gastroenterology & Hepatology | Opinion

    Although IBS and IBD are regarded as distinct entities, they do share features and symptoms. This Perspective explores the overlap between the two conditions, debating whether consideration of the similarities between IBS and IBD could improve treatment and inform future research.

    • Robin Spiller
    •  &  Giles Major
  • Nature Reviews Disease Primers | Primer

    Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high prevalence. Enck et al. describe the association between IBS and other gastrointestinal, somatic and psychiatric conditions, as well as the current view on the pathophysiology, and diagnostic and management options.

    • Paul Enck
    • , Qasim Aziz
    • , Giovanni Barbara
    • , Adam D. Farmer
    • , Shin Fukudo
    • , Emeran A. Mayer
    • , Beate Niesler
    • , Eamonn M. M. Quigley
    • , Mirjana Rajilić-Stojanović
    • , Michael Schemann
    • , Juliane Schwille-Kiuntke
    • , Magnus Simren
    • , Stephan Zipfel
    •  &  Robin C. Spiller

News & Research Highlights