Skip to main content

Advertisement

SpringerLink
Log in

Microbiota: a novel regulator of pain

  • Neurology and Preclinical Neurological Studies - Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Among the various regulators of the nervous system, the gut microbiota has been recently described to have the potential to modulate neuronal cells activation. While bacteria-derived products can induce aversive responses and influence pain perception, recent work suggests that “abnormal” microbiota is associated with neurological diseases such as Alzheimer’s, Parkinson’s disease or autism spectrum disorder (ASD). Here we review how the gut microbiota modulates afferent sensory neurons function and pain, highlighting the role of the microbiota/gut/brain axis in the control of behaviors and neurological diseases. We outline the changes in gut microbiota, known as dysbiosis, and their influence on painful gastrointestinal disorders. Furthermore, both direct host/microbiota interaction that implicates activation of “pain-sensing” neurons by metabolites, or indirect communication via immune activation is discussed. Finally, treatment options targeting the gut microbiota, including pre- or probiotics, will be proposed. Further studies on microbiota/nervous system interaction should lead to the identification of novel microbial ligands and host receptor-targeted drugs, which could ultimately improve chronic pain management and well-being.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ANS:

Autonomic nervous system

ASD:

Autistic spectrum disorder

CD:

Crohn’s disease

CGRP:

Calcitonin gene-related peptide

CHS:

Colonic hypersensitivity

CIPN:

Chemotherapy-induced peripheral neuropathy

CNS:

Central nervous system

CP:

Chronic prostatitis

CPPS:

Chronic pelvic pain syndrome

CpG:

Cytosine guanosine

DRG:

Dorsal root ganglion

EC:

Enterochromaffin cells

EPM:

Extracellular polymeric matrix

FD:

Functional dyspepsia

FODMAPs:

Fermentable oligo-, di-, monosaccharides and polyols

FMT:

Fecal microbiota transplantation

FPR:

Formyl peptide receptor

GABA:

Gamma-amino butyric acid

GF:

Germ-free

GPR41:

G-coupled receptor 41

HDAc:

Histone deacetylase

HPA:

Hypothalamic/pituitary/adrenal

IC:

Interstitial cystitis

IL:

Interleukin

IBD:

Inflammatory bowel disease

IBS:

Irritable bowel syndrome

LPS:

Lipopolysaccharide

Lypd8:

Ly6/Plaur domain-containing 8

LTA:

Lipoteichoic acid

MAM:

Microbial anti-inflammatory molecule

MAPKs:

Mitogen-activated protein kinases

NF-κB:

Nuclear factor-κB

NLR:

NOD-like receptor

NOD:

Nucleotide oligomerization domain receptor

PAMP:

Pathogen-associated molecular pattern

PGN:

Peptidoglycan

PI-IBS:

Post-infectious IBS

PRRs:

Pattern recognition receptor

PSA:

Polysaccharide A

SCFA:

Short-chain fatty acid

TIR:

Toll/interleukin-1 receptor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TRP:

Transient receptor potential channel

TRPA1:

Transient receptor potential ankyrin member 1

TRPM3:

Transient receptor potential melastatin member 3

TRPM8:

Transient receptor potential melastatin member 8

TRPV1:

Transient receptor potential vanilloid member 1

TRPV4:

Transient receptor potential vanilloid member 4

UC:

Ulcerative colitis

5-HT:

5-hydroxytryptamine or serotonin

References

  • Abernethy MG, Rosenfeld A, White JR, Mueller MG, Lewicky-Gaupp C, Kenton K (2017) Urinary microbiome and cytokine levels in women with interstitial cystitis. Obstet Gynecol 129:500–506

    Article  CAS  PubMed  Google Scholar 

  • Acosta C, Davies A (2008) Bacterial lipopolysaccharide regulates nociceptin expression in sensory neurons. J Neurosci Res 86:1077–1086

    Article  CAS  PubMed  Google Scholar 

  • Agostini S, Goubern M, Tondereau V, Salvador-Cartier C, Bezirard V, Lévèque M, Keränen H, Theodorou V, Bourdu-Naturel S, Goupil-Feuillerat N et al (2012) A marketed fermented dairy product containing Bifidobacterium lactis CNCM I-2494 suppresses gut hypersensitivity and colonic barrier disruption induced by acute stress in rats. Neurogastroenterol Motil 24:376-e172

    Article  PubMed  Google Scholar 

  • Aguilera M, Cerdà-Cuéllar M, Martínez V (2015) Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice. Gut Microbes 6:10–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmadmehrabi S, Tang WHW (2017) Gut microbiome and its role in cardiovascular diseases. Curr Opin Cardiol 32:761–766

    Article  PubMed  PubMed Central  Google Scholar 

  • Akbar A, Yiangou Y, Facer P, Walters JR, Anand P, Ghosh S (2008) Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut 57:923–929

    Article  CAS  PubMed  Google Scholar 

  • Alpizar YA, Boonen B, Sanchez A, Jung C, López-Requena A, Naert R, Steelant B, Luyts K, Plata C, De Vooght V et al (2017) TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells. Nat Commun 8:1059

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barajon I, Serrao G, Arnaboldi F, Opizzi E, Ripamonti G, Balsari A, Rumio C (2009) Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem 57:1013–1023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbara G, Scaioli E, Barbaro MR, Biagi E, Laghi L, Cremon C, Marasco G, Colecchia A, Picone G, Salfi N et al (2017) Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease. Gut 66:1252–1261

    Article  CAS  PubMed  Google Scholar 

  • Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R, Orsi RH, Wiedmann M, McDonough P, Kim SG et al (2007) Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn’s disease involving the ileum. ISME J 1:403–418

    Article  CAS  PubMed  Google Scholar 

  • Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR (2011) Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol 106:508–514 (quiz 515)

    Article  CAS  PubMed  Google Scholar 

  • Blandford LE, Johnston EL, Sanderson JD, Wade WG, Lax AJ (2019) Promoter orientation of the immunomodulatory Bacteroides fragilis capsular polysaccharide A (PSA) is off in individuals with inflammatory bowel disease (IBD). Gut Microbes 10:1–9

    Article  CAS  Google Scholar 

  • Böhn L, Störsrud S, Törnblom H, Bengtsson U, Simrén M (2013) Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 108:634–641

    Article  PubMed  CAS  Google Scholar 

  • Boonen B, Alpizar YA, Sanchez A, López-Requena A, Voets T, Talavera K (2018) Differential effects of lipopolysaccharide on mouse sensory TRP channels. Cell Calcium 73:72–81

    Article  CAS  PubMed  Google Scholar 

  • Botschuijver S, Roeselers G, Levin E, Jonkers DM, Welting O, Heinsbroek SEM, de Weerd HH, Boekhout T, Fornai M, Masclee AA et al (2017) Intestinal fungal dysbiosis is associated with visceral hypersensitivity in patients with irritable bowel syndrome and rats. Gastroenterology 153:1026–1039

    Article  PubMed  Google Scholar 

  • Braundmeier-Fleming A, Russell NT, Yang W, Nas MY, Yaggie RE, Berry M, Bachrach L, Flury SC, Marko DS, Bushell CB et al (2016) Stool-based biomarkers of interstitial cystitis/bladder pain syndrome. Sci Rep 6:26083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brint EK, MacSharry J, Fanning A, Shanahan F, Quigley EMM (2011) Differential expression of toll-like receptors in patients with irritable bowel syndrome. Am J Gastroenterol 106:329–336

    Article  CAS  PubMed  Google Scholar 

  • Cario E, Podolsky DK (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68:7010–7017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Casén C, Vebø HC, Sekelja M, Hegge FT, Karlsson MK, Ciemniejewska E, Dzankovic S, Frøyland C, Nestestog R, Engstrand L et al (2015) Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment Pharmacol Ther 42:71–83

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Castiglione F, Rispo A, Di Girolamo E, Cozzolino A, Manguso F, Grassia R, Mazzacca G (2003) Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn’s disease. Aliment Pharmacol Ther 18:1107–1112

    Article  CAS  PubMed  Google Scholar 

  • Cenac N, Altier C, Motta J-P, d’Aldebert E, Galeano S, Zamponi GW, Vergnolle N (2010) Potentiation of TRPV4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity. Gut 59:481–488

    Article  CAS  PubMed  Google Scholar 

  • Chandrasekharan B, Saeedi BJ, Alam A, Houser M, Srinivasan S, Tansey M, Jones R, Nusrat A, Neish AS (2019) Interactions between commensal bacteria and enteric neurons, via FPR1 induction of ROS, increase gastrointestinal motility in mice. Gastroenterology 157:179–192

    Article  CAS  PubMed  Google Scholar 

  • Chassard C, Dapoigny M, Scott KP, Crouzet L, Del Homme C, Marquet P, Martin JC, Pickering G, Ardid D, Eschalier A et al (2012) Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther 35:828–838

    Article  CAS  PubMed  Google Scholar 

  • Chehoud C, Albenberg LG, Judge C, Hoffmann C, Grunberg S, Bittinger K, Baldassano RN, Lewis JD, Bushman FD, Wu GD (2015) Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 21:1948–1956

    Article  PubMed  Google Scholar 

  • Chiu IM, Heesters BA, Ghasemlou N, Von Hehn CA, Zhao F, Tran J, Wainger B, Strominger A, Muralidharan S, Horswill AR et al (2013) Bacteria activate sensory neurons that modulate pain and inflammation. Nature 501:52–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choung RS, Ruff KC, Malhotra A, Herrick L, Locke GR, Harmsen WS, Zinsmeister AR, Talley NJ, Saito YA (2011) Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture. Aliment Pharmacol Ther 33:1059–1067

    Article  CAS  PubMed  Google Scholar 

  • Cremon C, Stanghellini V, Pallotti F, Fogacci E, Bellacosa L, Morselli-Labate AM, Paccapelo A, Di Nardo G, Cogliandro RF, De Giorgio R et al (2014) Salmonella gastroenteritis during childhood is a risk factor for irritable bowel syndrome in adulthood. Gastroenterology 147:69–77

    Article  PubMed  Google Scholar 

  • Crouzet L, Gaultier E, Del Homme C, Cartier C, Delmas E, Dapoigny M, Fioramonti J, Bernalier-Donadille A (2013) The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota. Neurogastroenterol Motil 25:e272–e282

    Article  CAS  PubMed  Google Scholar 

  • Crowell MD (2004) Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol 141:1285–1293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13:701–712

    Article  CAS  PubMed  Google Scholar 

  • Da Silva S, Robbe-Masselot C, Ait-Belgnaoui A, Mancuso A, Mercade-Loubière M, Salvador-Cartier C, Gillet M, Ferrier L, Loubière P, Dague E et al (2014) Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment. Am J Physiol Gastrointest Liver Physiol 307:G420–G429

    Article  PubMed  CAS  Google Scholar 

  • Daelemans S, Peeters L, Hauser B, Vandenplas Y (2018) Recent advances in understanding and managing infantile colic. F1000Research 7(F1000Faculty Rev):1426

  • Dai C, Guandalini S, Zhao D-H, Jiang M (2012) Antinociceptive effect of VSL#3 on visceral hypersensitivity in a rat model of irritable bowel syndrome: a possible action through nitric oxide pathway and enhance barrier function. Mol Cell Biochem 362:43–53

    Article  CAS  PubMed  Google Scholar 

  • Darbro BW, Petroelje BK, Doern GV (2009) Lactobacillus delbrueckii as the cause of urinary tract infection. J Clin Microbiol 47:275–277

    Article  PubMed  Google Scholar 

  • De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R (2013) Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 8:e76993

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Logu F, Nassini R, Landini L, Geppetti P (2019) Pathways of CGRP Release from Primary Sensory Neurons. Handb Exp Pharmacol 255:65–84

    Article  PubMed  CAS  Google Scholar 

  • De Palma G, Lynch MDJ, Lu J, Dang VT, Deng Y, Jury J, Umeh G, Miranda PM, Pigrau Pastor M, Sidani S et al (2017) Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice. Sci Transl, Med, p 9

    Google Scholar 

  • de Weerth C, Fuentes S, de Vos WM (2013) Crying in infants: on the possible role of intestinal microbiota in the development of colic. Gut Microbes 4:416–421

    Article  PubMed  PubMed Central  Google Scholar 

  • Derrien M, Vaughan EE, Plugge CM, de Vos WM (2004) Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 54:1469–1476

    Article  CAS  PubMed  Google Scholar 

  • Didari T, Mozaffari S, Nikfar S, Abdollahi M (2015) Effectiveness of probiotics in irritable bowel syndrome: updated systematic review with meta-analysis. World J Gastroenterol 21:3072–3084

    Article  PubMed  PubMed Central  Google Scholar 

  • Diogenes A, Ferraz CCR, Akopian AN, Henry MA, Hargreaves KM (2011) LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res 90:759–764

    Article  CAS  PubMed  Google Scholar 

  • Distrutti E, Cipriani S, Mencarelli A, Renga B, Fiorucci S (2013) Probiotics VSL#3 protect against development of visceral pain in murine model of irritable bowel syndrome. PLoS One 8:e63893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donohoe DR, Holley D, Collins LB, Montgomery SA, Whitmore AC, Hillhouse A, Curry KP, Renner SW, Greenwalt A, Ryan EP et al (2014) A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov 4:1387–1397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du L-J, Chen B-R, Kim JJ, Kim S, Shen J-H, Dai N (2016) Helicobacter pylori eradication therapy for functional dyspepsia: systematic review and meta-analysis. World J Gastroenterol 22:3486–3495

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Duboc H, Rainteau D, Rajca S, Humbert L, Farabos D, Maubert M, Grondin V, Jouet P, Bouhassira D, Seksik P et al (2012) Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil 24(513–520):e246–e247

    Google Scholar 

  • Duncan SH, Louis P, Flint HJ (2004) Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Env Microbiol 70:5810–5817

    Article  CAS  Google Scholar 

  • Dutta SK, Verma S, Jain V, Surapaneni BK, Vinayek R, Phillips L, Nair PP (2019) Parkinson’s disease: the emerging role of gut dysbiosis, antibiotics, probiotics, and fecal microbiota transplantation. J Neurogastroenterol Motil 25:363–376

    Article  PubMed  PubMed Central  Google Scholar 

  • Enck P, Mazurak N (2018) Dysbiosis in functional bowel disorders. Ann Nutr Metab 72:296–306

    Article  CAS  PubMed  Google Scholar 

  • Enck P, Aziz Q, Barbara G, Farmer AD, Fukudo S, Mayer EA, Niesler B, Quigley EMM, Rajilić-Stojanović M, Schemann M et al (2016) Irritable bowel syndrome. Nat Rev Dis Primer 2:16014

    Article  Google Scholar 

  • Eutamene H, Lamine F, Chabo C, Theodorou V, Rochat F, Bergonzelli GE, Corthésy-Theulaz I, Fioramonti J, Bueno L (2007) Synergy between Lactobacillus paracasei and its bacterial products to counteract stress-induced gut permeability and sensitivity increase in rats. J Nutr 137:1901–1907

    Article  CAS  PubMed  Google Scholar 

  • Eutamène H, Garcia-Rodenas CL, Yvon S, d’Aldebert E, Foata F, Berger B, Sauser J, Theodorou V, Bergonzelli G, Mas E (2017) Luminal contents from the gut of colicky infants induce visceral hypersensitivity in mice. Neurogastroenterol Motil, Soc, p 29

    Google Scholar 

  • Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D et al (2016) Population-level analysis of gut microbiome variation. Science 352:560–564

    Article  CAS  PubMed  Google Scholar 

  • Farup PG, Rudi K, Hestad K (2016) Faecal short-chain fatty acids—a diagnostic biomarker for irritable bowel syndrome? BMC Gastroenterol 16:51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Feehily C, Karatzas KAG (2013) Role of glutamate metabolism in bacterial responses towards acid and other stresses. J Appl Microbiol 114:11–24

    Article  CAS  PubMed  Google Scholar 

  • Ferraz CCR, Henry MA, Hargreaves KM, Diogenes A (2011) Lipopolysaccharide from Porphyromonas gingivalis sensitizes capsaicin-sensitive nociceptors. J Endod 37:45–48

    Article  PubMed  PubMed Central  Google Scholar 

  • Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A (2014) Gut microbiota and metabolic syndrome. World J Gastroenterol 20:16079–16094

    Article  PubMed  PubMed Central  Google Scholar 

  • Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, Youn E, Summanen PH, Granpeesheh D, Dixon D et al (2010) Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe 16:444–453

    Article  CAS  PubMed  Google Scholar 

  • Ford AC, Harris LA, Lacy BE, Quigley EMM, Moayyedi P (2018) Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Aliment Pharmacol Ther 48:1044–1060

    Article  PubMed  Google Scholar 

  • Fox M, Knorr DA, Haptonstall KM (2019) Alzheimer’s disease and symbiotic microbiota: an evolutionary medicine perspective. Ann N Y Acad Sci 1449:3–24

    PubMed  Google Scholar 

  • Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104:13780–13785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukata M, Abreu MT (2007) TLR4 signalling in the intestine in health and disease. Biochem Soc Trans 35:1473–1478

    Article  CAS  PubMed  Google Scholar 

  • Fukata M, Abreu MT (2009) Pathogen recognition receptors, cancer and inflammation in the gut. Curr Opin Pharmacol 9:680–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gargari G, Taverniti V, Gardana C, Cremon C, Canducci F, Pagano I, Barbaro MR, Bellacosa L, Castellazzi AM, Valsecchi C et al (2018) Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome. Environ Microbiol 20:3201–3213

    Article  CAS  PubMed  Google Scholar 

  • Gilbert JA, Krajmalnik-Brown R, Porazinska DL, Weiss SJ, Knight R (2013) Toward effective probiotics for autism and other neurodevelopmental disorders. Cell 155:1446–1448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG (2014) A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 146:67–75.e5

    Article  CAS  PubMed  Google Scholar 

  • Halpin SJ, Ford AC (2012) Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 107:1474–1482

    Article  PubMed  Google Scholar 

  • Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB et al (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941–1967

    Article  CAS  PubMed  Google Scholar 

  • Hoban AE, Moloney RD, Golubeva AV, McVey Neufeld KA, O’Sullivan O, Patterson E, Stanton C, Dinan TG, Clarke G, Cryan JF (2016) Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat. Neuroscience 339:463–477

    Article  CAS  PubMed  Google Scholar 

  • Holingue C, Newill C, Lee L-C, Pasricha PJ, Daniele Fallin M (2018) Gastrointestinal symptoms in autism spectrum disorder: a review of the literature on ascertainment and prevalence. Autism Res 11:24–36

    Article  PubMed  Google Scholar 

  • Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF et al (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155:1451–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu C-C, Okumura R, Takeda K (2017) Human LYPD8 protein inhibits motility of flagellated bacteria. Inflamm. Regen. 37:23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hungin APS, Mulligan C, Pot B, Whorwell P, Agréus L, Fracasso P, Lionis C, Mendive J, de Foy J-MP, Rubin G et al (2013) Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice—an evidence-based international guide. Aliment Pharmacol Ther 38:864–886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Igarashi M, Nakae H, Matsuoka T, Takahashi S, Hisada T, Tomita J, Koga Y (2017) Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia. BMJ Open Gastroenterol 4:e000144

    Article  PubMed  PubMed Central  Google Scholar 

  • Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M et al (2012) Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336:1314–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inohara N, Chamaillard M, McDonald C, Nuñez G (2005) NOD-LRR PROTEINS: role in host-microbial interactions and inflammatory disease. Annu Rev Biochem 74:355–383

    Article  CAS  PubMed  Google Scholar 

  • Inoue D, Kimura I, Wakabayashi M, Tsumoto H, Ozawa K, Hara T, Takei Y, Hirasawa A, Ishihama Y, Tsujimoto G (2012) Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation. FEBS Lett 586:1547–1554

    Article  CAS  PubMed  Google Scholar 

  • Jahng J, Jung IS, Choi EJ, Conklin JL, Park H (2012) The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time. Neurogastroenterol Motil 24(185–190):e92

    Google Scholar 

  • Jalanka-Tuovinen J, Salojärvi J, Salonen A, Immonen O, Garsed K, Kelly FM, Zaitoun A, Palva A, Spiller RC, de Vos WM (2014) Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome. Gut 63:1737–1745

    Article  PubMed  Google Scholar 

  • Janssens Y, Wynendaele E, Verbeke F, Debunne N, Gevaert B, Audenaert K, Van DeWiele C, De Spiegeleer B (2018) Screening of quorum sensing peptides for biological effects in neuronal cells. Peptides 101:150–156

    Article  CAS  PubMed  Google Scholar 

  • Jeffery IB, O’Toole PW, Öhman L, Claesson MJ, Deane J, Quigley EMM, Simrén M (2012) An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 61:997–1006

    Article  PubMed  Google Scholar 

  • Johnson AC, Greenwood-Van Meerveld B, McRorie J (2011) Effects of Bifidobacterium infantis 35624 on post-inflammatory visceral hypersensitivity in the rat. Dig Dis Sci 56:3179–3186

    Article  PubMed  Google Scholar 

  • Jung T-H, Park JH, Jeon W-M, Han K-S (2015) Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretion and MAPK signaling pathway. Nutr Res Pract 9:343–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamiya T, Wang L, Forsythe P, Goettsche G, Mao Y, Wang Y, Tougas G, Bienenstock J (2006) Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague-Dawley rats. Gut 55:191–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang D-W, Park JG, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown R (2013) Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children. PLoS One 8:e68322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang S-S, Sim J-R, Yun C-H, Han SH (2016) Lipoteichoic acids as a major virulence factor causing inflammatory responses via Toll-like receptor 2. Arch Pharm Res 39:1519–1529

    Article  CAS  PubMed  Google Scholar 

  • Kannampalli P, Shaker R, Sengupta JN (2011) Colonic butyrate- algesic or analgesic? Neurogastroenterol. Motil 23:975–979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384

    Article  CAS  PubMed  Google Scholar 

  • Kerckhoffs APM, Samsom M, van der Rest ME, de Vogel J, Knol J, Ben-Amor K, Akkermans LMA (2009) Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients. World J Gastroenterol 15:2887–2892

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim G, Deepinder F, Morales W, Hwang L, Weitsman S, Chang C, Gunsalus R, Pimentel M (2012) Methanobrevibacter smithii is the predominant methanogen in patients with constipation-predominant IBS and methane on breath. Dig Dis Sci 57:3213–3218

    Article  CAS  PubMed  Google Scholar 

  • Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, Kobayashi M, Hirasawa A, Tsujimoto G (2011) Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci 108:8030–8035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klem F, Wadhwa A, Prokop LJ, Sundt WJ, Farrugia G, Camilleri M, Singh S, Grover M (2017) Prevalence, Risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: a systematic review and meta-analysis. Gastroenterology 152:1042–1054.e1

    Article  PubMed  Google Scholar 

  • Konstantareas MM, Homatidis S (1987) Ear infections in autistic and normal children. J Autism Dev Disord 17:585–594

    Article  CAS  PubMed  Google Scholar 

  • Kowalcyk BK, Smeets HM, Succop PA, De Wit NJ, Havelaar AH (2014) Relative risk of irritable bowel syndrome following acute gastroenteritis and associated risk factors. Epidemiol Infect 142:1259–1268

    Article  CAS  PubMed  Google Scholar 

  • Krsmanovic A, Tripp DA, Nickel JC, Shoskes DA, Pontari M, Litwin MS, McNaughton-Collins MF (2014) Psychosocial mechanisms of the pain and quality of life relationship for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Can Urol Assoc J 8:403–408

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar H, Kawai T, Akira S (2009) Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388:621–625

    Article  CAS  PubMed  Google Scholar 

  • Kvasnovsky CL, Leong LEX, Choo JM, Abell GCJ, Papagrigoriadis S, Bruce KD, Rogers GB (2018) Clinical and symptom scores are significantly correlated with fecal microbiota features in patients with symptomatic uncomplicated diverticular disease: a pilot study. Eur J Gastroenterol Hepatol 30:107–112

    Article  CAS  PubMed  Google Scholar 

  • Lai M-C, Lombardo MV, Baron-Cohen S (2014) Autism. Lancet Lond Engl 383:896–910

    Article  Google Scholar 

  • Lai NY, Mills K, Chiu IM (2017) Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence. J Intern Med 282:5–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Nevé B, Posserud I, Böhn L, Guyonnet D, Rondeau P, Tillisch K, Naliboff B, Mayer EA, Simrén M (2013) A combined nutrient and lactulose challenge test allows symptom-based clustering of patients with irritable bowel syndrome. Am J Gastroenterol 108:786–795

    Article  PubMed  CAS  Google Scholar 

  • Lee YY, Annamalai C, Rao SSC (2017) Post-infectious irritable bowel syndrome. Curr Gastroenterol Rep 19:56

    Article  PubMed  Google Scholar 

  • Ley RE, Gewirtz AT (2016) Corralling colonic flagellated microbiota. N Engl J Med 375:85–87

    Article  PubMed  Google Scholar 

  • Liu T, Gao Y-J, Ji R-R (2012) Emerging role of Toll-like receptors in the control of pain and itch. Neurosci Bull 28:131–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Long MD, Drossman DA (2010) Inflammatory bowel disease, irritable bowel syndrome, or what? A challenge to the functional-organic dichotomy. Am J Gastroenterol 105:1796–1798

    Article  PubMed  Google Scholar 

  • Lönnfors S, Vermeire S, Greco M, Hommes D, Bell C, Avedano L (2014) IBD and health-related quality of life—discovering the true impact. J Crohns Colitis 8:1281–1286

    Article  PubMed  Google Scholar 

  • Louis P, Young P, Holtrop G, Flint HJ (2010) Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol 12:304–314

    Article  CAS  PubMed  Google Scholar 

  • Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489:220–230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu Y-C, Yeh W-C, Ohashi PS (2008) LPS/TLR4 signal transduction pathway. Cytokine 42:145–151

    Article  CAS  PubMed  Google Scholar 

  • Luczynski P, Tramullas M, Viola M, Shanahan F, Clarke G, O’Mahony S, Dinan TG, Cryan JF (2017) Microbiota regulates visceral pain in the mouse. ELife 6:e25887

    Article  PubMed  PubMed Central  Google Scholar 

  • Luna RA, Oezguen N, Balderas M, Venkatachalam A, Runge JK, Versalovic J, Veenstra-VanderWeele J, Anderson GM, Savidge T, Williams KC (2017) Distinct microbiome-neuroimmune signatures correlate with functional abdominal pain in children with autism spectrum disorder. Cell Mol Gastroenterol Hepatol 3:218–230

    Article  PubMed  Google Scholar 

  • Lyra A, Rinttilä T, Nikkilä J, Krogius-Kurikka L, Kajander K, Malinen E, Mättö J, Mäkelä L, Palva A (2009) Diarrhoea-predominant irritable bowel syndrome distinguishable by 16S rRNA gene phylotype quantification. World J Gastroenterol 15:5936–5945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyte M (2011) Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. BioEssays News Rev. Mol Cell Dev Biol 33:574–581

    CAS  Google Scholar 

  • Macfarlane GT, Macfarlane S (2012) Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int 95(1):50–60

    Article  CAS  PubMed  Google Scholar 

  • Magistro G (2019) Urological infections: “the time for change is now”. Eur Urol Focus 5:1

    Article  PubMed  Google Scholar 

  • Malinen E, Rinttilä T, Kajander K, Mättö J, Kassinen A, Krogius L, Saarela M, Korpela R, Palva A (2005) Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am J Gastroenterol 100:373–382

    Article  CAS  PubMed  Google Scholar 

  • Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P et al (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55:205–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mao Y-K, Kasper DL, Wang B, Forsythe P, Bienenstock J, Kunze WA (2013) Bacteroides fragilis polysaccharide A is necessary and sufficient for acute activation of intestinal sensory neurons. Nat Commun 4:1465

    Article  PubMed  CAS  Google Scholar 

  • Marion E, Song O-R, Christophe T, Babonneau J, Fenistein D, Eyer J, Letournel F, Henrion D, Clere N, Paille V et al (2014) Mycobacterial toxin induces analgesia in Buruli ulcer by targeting the angiotensin pathways. Cell 157:1565–1576

    Article  CAS  PubMed  Google Scholar 

  • Matsunami M, Tarui T, Mitani K, Nagasawa K, Fukushima O, Okubo K, Yoshida S, Takemura M, Kawabata A (2009) Luminal hydrogen sulfide plays a pronociceptive role in mouse colon. Gut 58:751–761

    Article  CAS  PubMed  Google Scholar 

  • Mayer EA, Tillisch K, Gupta A (2015) Gut/brain axis and the microbiota. J. Clin. Invest. 125:926–938

    Article  PubMed  PubMed Central  Google Scholar 

  • McCusker RH, Kelley KW (2013) Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol 216:84–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKernan DP, Fitzgerald P, Dinan TG, Cryan JF (2010) The probiotic Bifidobacterium infantis 35624 displays visceral antinociceptive effects in the rat. Neurogastroenterol Motil 22(1029–1035):e268

    Google Scholar 

  • Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449:819–826

    Article  CAS  PubMed  Google Scholar 

  • Meseguer V, Alpizar YA, Luis E, Tajada S, Denlinger B, Fajardo O, Manenschijn J-A, Fernández-Peña C, Talavera A, Kichko T et al (2014) TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins. Nat. Commun. 5:3125

    Article  PubMed  CAS  Google Scholar 

  • Miquel S, Martín R, Lashermes A, Gillet M, Meleine M, Gelot A, Eschalier A, Ardid D, Bermúdez-Humarán LG, Sokol H et al (2016) Anti-nociceptive effect of Faecalibacterium prausnitzii in non-inflammatory IBS-like models. Sci. Rep. 6:19399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EMM (2010) The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 59:325–332

    Article  CAS  PubMed  Google Scholar 

  • Morrison DJ, Preston T (2016) Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 7:189–200

    Article  PubMed  PubMed Central  Google Scholar 

  • Morrison DJ, Mackay WG, Edwards CA, Preston T, Dodson B, Weaver LT (2006) Butyrate production from oligofructose fermentation by the human faecal flora: what is the contribution of extracellular acetate and lactate? Br J Nutr 96:570–577

    CAS  PubMed  Google Scholar 

  • Mukhopadhya I, Hansen R, Meharg C, Thomson JM, Russell RK, Berry SH, El-Omar EM, Hold GL (2015) The fungal microbiota of de-novo paediatric inflammatory bowel disease. Microbes Infect 17:304–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakae H, Tsuda A, Matsuoka T, Mine T, Koga Y (2016) Gastric microbiota in the functional dyspepsia patients treated with probiotic yogurt. BMJ Open Gastroenterol. 3:e000109

    Article  PubMed  PubMed Central  Google Scholar 

  • Nickel JC, Stephens A, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Ehrlich GD, MAPP Research Network (2016) Assessment of the lower urinary tract microbiota during symptom flare in women with urologic chronic pelvic pain syndrome: A MAPP Network Study. J. Urol. 195:356–362

    Article  PubMed  Google Scholar 

  • Nickel JC, Stephens-Shields AJ, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Henderson JP, Sen B, Krol JE, Ehrlich GD et al (2019) A culture-independent analysis of the microbiota of female interstitial cystitis/bladder pain syndrome participants in the MAPP research network. J. Clin, Med, p 8

    Google Scholar 

  • Niehus R, Lord C (2006) Early medical history of children with autism spectrum disorders. J Dev Behav Pediatr JDBP 27:S120–S127

    Article  PubMed  Google Scholar 

  • Nielsen HL, Engberg J, Ejlertsen T, Nielsen H (2014) Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection. Scand J Gastroenterol 49:545–551

    Article  PubMed  Google Scholar 

  • Nøhr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS, Husted AS, Sichlau RM, Grunddal KV, Seier Poulsen S, Han S et al (2013) GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology 154:3552–3564

    Article  PubMed  CAS  Google Scholar 

  • Nøhr MK, Egerod KL, Christiansen SH, Gille A, Offermanns S, Schwartz TW, Møller M (2015) Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience 290:126–137

    Article  PubMed  CAS  Google Scholar 

  • Nourrisson C, Scanzi J, Pereira B, NkoudMongo C, Wawrzyniak I, Cian A, Viscogliosi E, Livrelli V, Delbac F, Dapoigny M et al (2014) Blastocystis is associated with decrease of fecal microbiota protective bacteria: comparative analysis between patients with irritable bowel syndrome and control subjects. PLoS One 9:e111868

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • O’Keeffe M, Jansen C, Martin L, Williams M, Seamark L, Staudacher HM, Irving PM, Whelan K, Lomer MC (2018) Long-term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome. Neurogastroenterol. Motil, Soc, p 30

    Google Scholar 

  • O’Mahony SM, Tramullas M, Fitzgerald P, Cryan JF (2012) Rodent models of colorectal distension. Curr. Protoc. Neurosci. 61:9.40 (Chapter 9)

    Google Scholar 

  • O’Mahony SM, Clarke G, McKernan DP, Bravo JA, Dinan TG, Cryan JF (2013) Differential visceral nociceptive, behavioural and neurochemical responses to an immune challenge in the stress-sensitive Wistar Kyoto rat strain. Behav Brain Res 253:310–317

    Article  CAS  Google Scholar 

  • O’Mahony SM, Felice VD, Nally K, Savignac HM, Claesson MJ, Scully P, Woznicki J, Hyland NP, Shanahan F, Quigley EM et al (2014) Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience 277:885–901

    Article  PubMed  CAS  Google Scholar 

  • O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF (2015) Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res 277:32–48

    Article  PubMed  CAS  Google Scholar 

  • Ochoa-Cortes F, Ramos-Lomas T, Miranda-Morales M, Spreadbury I, Ibeakanma C, Barajas-Lopez C, Vanner S (2010) Bacterial cell products signal to mouse colonic nociceptive dorsal root ganglia neurons. Am J Physiol Gastrointest Liver Physiol 299:G723–G732

    Article  CAS  PubMed  Google Scholar 

  • Okumura R, Takeda K (2018) Maintenance of intestinal homeostasis by mucosal barriers. Inflamm. Regen. 38:5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Okumura R, Kurakawa T, Nakano T, Kayama H, Kinoshita M, Motooka D, Gotoh K, Kimura T, Kamiyama N, Kusu T et al (2016) Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature 532:117–121

    Article  CAS  PubMed  Google Scholar 

  • Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Fölsch UR, Timmis KN, Schreiber S (2004) Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53:685–693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ott SJ, Kühbacher T, Musfeldt M, Rosenstiel P, Hellmig S, Rehman A, Drews O, Weichert W, Timmis KN, Schreiber S (2008) Fungi and inflammatory bowel diseases: alterations of composition and diversity. Scand J Gastroenterol 43:831–841

    Article  CAS  PubMed  Google Scholar 

  • Parkes GC, Rayment NB, Hudspith BN, Petrovska L, Lomer MC, Brostoff J, Whelan K, Sanderson JD (2012) Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome. Neurogastroenterol Motil 24:31–39

    Article  CAS  PubMed  Google Scholar 

  • Pärtty A, Luoto R, Kalliomäki M, Salminen S, Isolauri E (2013) Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. J. Pediatr. 163:1272–1277.e1–2

    Article  PubMed  Google Scholar 

  • Pérez-Berezo T, Pujo J, Martin P, Faouder PL, Galano J-M, Guy A, Knauf C, Tabet JC, Tronnet S, Barreau F et al (2017) Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917. Nat. Commun. 8:1314

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Piche T, Ducrotté P, Sabate JM, Coffin B, Zerbib F, Dapoigny M, Hua M, Marine-Barjoan E, Dainese R, Hébuterne X (2010) Impact of functional bowel symptoms on quality of life and fatigue in quiescent Crohn disease and irritable bowel syndrome. Neurogastroenterol Motil 22:626-e174

    Article  PubMed  Google Scholar 

  • Pimentel M, Lin HC, Enayati P, van den Burg B, Lee H-R, Chen JH, Park S, Kong Y, Conklin J (2006) Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity. Am J Physiol Gastrointest Liver Physiol 290:G1089–G1095

    Article  CAS  PubMed  Google Scholar 

  • Pinho-Ribeiro FA, Verri WA, Chiu IM (2017) Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol 38:5–19

    Article  CAS  PubMed  Google Scholar 

  • Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L et al (2017) A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med 23:107–113

    Article  CAS  PubMed  Google Scholar 

  • Ponnusamy K, Choi JN, Kim J, Lee S-Y, Lee CH (2011) Microbial community and metabolomic comparison of irritable bowel syndrome faeces. J Med Microbiol 60:817–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Porter CK, Cash BD, Pimentel M, Akinseye A, Riddle MS (2012) Risk of inflammatory bowel disease following a diagnosis of irritable bowel syndrome. BMC Gastroenterol. 12:55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Posserud I, Strid H, Störsrud S, Törnblom H, Svensson U, Tack J, Van Oudenhove L, Simrén M (2013) Symptom pattern following a meal challenge test in patients with irritable bowel syndrome and healthy controls. United Eur. Gastroenterol. J. 1:358–367

    Article  Google Scholar 

  • Pourmand H, Esmaillzadeh A (2017) Consumption of a low fermentable oligo-, di-, mono-saccharides, and polyols diet and irritable bowel syndrome: a systematic review. Int. J. Prev. Med. 8:104

    Article  PubMed  PubMed Central  Google Scholar 

  • Pozuelo M, Panda S, Santiago A, Mendez S, Accarino A, Santos J, Guarner F, Azpiroz F, Manichanh C (2015) Reduction of butyrate- and methane-producing microorganisms in patients with irritable bowel syndrome. Sci. Rep. 5:12693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qi J, Buzas K, Fan H, Cohen JI, Wang K, Mont E, Klinman D, Oppenheim JJ, Howard OMZ (2011) Painful pathways induced by TLR stimulation of dorsal root ganglion neurons. J. Immunol. Baltim. Md 1950(186):6417–6426

    Google Scholar 

  • Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, Miquel S, Carlier L, Bermúdez-Humarán LG, Pigneur B et al (2016) Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut 65:415–425

    Article  PubMed  CAS  Google Scholar 

  • Rajilić-Stojanović M, de Vos WM (2014) The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiol Rev 38:996–1047

    Article  PubMed  CAS  Google Scholar 

  • Reigstad CS, Salmonson CE, Rainey JF, Szurszewski JH, Linden DR, Sonnenburg JL, Farrugia G, Kashyap PC (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29:1395–1403

    Article  CAS  PubMed  Google Scholar 

  • Ren K, Dubner R (2010) Interactions between the immune and nervous systems in pain. Nat Med 16:1267–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rigsbee L, Agans R, Shankar V, Kenche H, Khamis HJ, Michail S, Paliy O (2012) Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 107:1740–1751

    Article  PubMed  Google Scholar 

  • Ringel Y, Ringel-Kulka T (2015) The intestinal microbiota and irritable bowel syndrome. J Clin Gastroenterol 49(Suppl 1):S56–S59

    Article  CAS  PubMed  Google Scholar 

  • Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilán CG, Salazar N (2016) Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 7:185

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodiño-Janeiro BK, Vicario M, Alonso-Cotoner C, Pascua-García R, Santos J (2018) A review of microbiota and irritable bowel syndrome: future in therapies. Adv. Ther. 35:289–310

    Article  PubMed  PubMed Central  Google Scholar 

  • Rondanelli M, Riva A, Morazzoni P, Allegrini P, Faliva MA, Naso M, Miccono A, Peroni G, Degli Agosti I, Perna S (2017) The effect and safety of highly standardized Ginger (Zingiber officinale) and Echinacea (Echinacea angustifolia) extract supplementation on inflammation and chronic pain in NSAIDs poor responders. A pilot study in subjects with knee arthrosis. Nat Prod Res 31:1309–1313

    Article  CAS  PubMed  Google Scholar 

  • Rooks MG, Garrett WS (2016) Gut microbiota, metabolites and host immunity. Nat Rev Immunol 16:341–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rooks MG, Veiga P, Wardwell-Scott LH, Tickle T, Segata N, Michaud M, Gallini CA, Beal C, van Hylckama-Vlieg JET, Ballal SA et al (2014) Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission. ISME J 8:1403–1417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rossi O, Khan MT, Schwarzer M, Hudcovic T, Srutkova D, Duncan SH, Stolte EH, Kozakova H, Flint HJ, Samsom JN et al (2015) Faecalibacterium prausnitzii strain HTF-F and its extracellular polymeric matrix attenuate clinical parameters in DSS-induced colitis. PLoS One 10:e0123013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rostami A, Riahi SM, Haghighi A, Saber V, Armon B, Seyyedtabaei SJ (2017) The role of Blastocystis sp. and Dientamoeba fragilis in irritable bowel syndrome: a systematic review and meta-analysis. Parasitol Res 116:2361–2371

    Article  PubMed  Google Scholar 

  • Rueda-Ruzafa L, Cruz F, Roman P, Cardona D (2019) Gut microbiota and neurological effects of glyphosate. Neurotoxicology 75:1–8

    Article  CAS  PubMed  Google Scholar 

  • Saulnier DM, Riehle K, Mistretta T-A, Diaz M-A, Mandal D, Raza S, Weidler EM, Qin X, Coarfa C, Milosavljevic A et al (2011) Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 141:1782–1791

    Article  CAS  PubMed  Google Scholar 

  • Savino F, Cresi F, Pautasso S, Palumeri E, Tullio V, Roana J, Silvestro L, Oggero R (2004) Intestinal microflora in breastfed colicky and non-colicky infants. Acta Paediatr Oslo Nor 1992(93):825–829

    Article  Google Scholar 

  • Schumann D, Langhorst J, Dobos G, Cramer H (2018) Randomised clinical trial: yoga vs a low-FODMAP diet in patients with irritable bowel syndrome. Aliment Pharmacol Ther 47:203–211

    Article  CAS  PubMed  Google Scholar 

  • Sekirov I, Russell SL, Antunes LCM, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904

    Article  CAS  PubMed  Google Scholar 

  • Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLoS Biol 14:e1002533

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155:2461–2470

    Article  PubMed  Google Scholar 

  • Sessenwein JL, Baker CC, Pradhananga S, Maitland ME, Petrof EO, Allen-Vercoe E, Noordhof C, Reed DE, Vanner SJ, Lomax AE (2017) Protease-mediated suppression of DRG neuron excitability by commensal bacteria. J Neurosci 37:11758–11768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen S, Lim G, You Z, Ding W, Huang P, Ran C, Doheny J, Caravan P, Tate S, Hu K et al (2017) Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci 20:1213–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shepherd SJ, Parker FC, Muir JG, Gibson PR (2008) Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol 6:765–771

    Article  CAS  PubMed  Google Scholar 

  • Shoskes DA, Macoska JA (2017) Preface to the human microbiome in urologic health and disease. Ann Transl Med 5:27

    Article  PubMed  PubMed Central  Google Scholar 

  • Shoskes DA, Altemus J, Polackwich AS, Tucky B, Wang H, Eng C (2016) The urinary microbiome differs significantly between patients with chronic prostatitis/chronic pelvic pain syndrome and controls as well as between patients with different clinical phenotypes. Urology 92:26–32

    Article  PubMed  Google Scholar 

  • Siddiqui H, Lagesen K, Nederbragt AJ, Jeansson SL, Jakobsen KS (2012) Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol 12:205

    Article  PubMed  PubMed Central  Google Scholar 

  • Simrén M, Tack J (2018) New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat. Rev. Gastroenterol. Hepatol. 15:589–605

    Article  PubMed  CAS  Google Scholar 

  • Sokol H, Seksik P, Rigottier-Gois L, Lay C, Lepage P, Podglajen I, Marteau P, Doré J (2006) Specificities of the fecal microbiota in inflammatory bowel disease. Inflamm Bowel Dis 12:106–111

    Article  PubMed  Google Scholar 

  • Sokol H, Leducq V, Aschard H, Pham H-P, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I et al (2017) Fungal microbiota dysbiosis in IBD. Gut 66:1039–1048

    Article  CAS  PubMed  Google Scholar 

  • Spiller RC, Humes DJ, Campbell E, Hastings M, Neal KR, Dukes GE, Whorwell PJ (2010) The Patient Health Questionnaire 12 Somatic Symptom scale as a predictor of symptom severity and consulting behaviour in patients with irritable bowel syndrome and symptomatic diverticular disease. Aliment Pharmacol Ther 32:811–820

    Article  CAS  PubMed  Google Scholar 

  • Staudacher HM, Lomer MCE, Farquharson FM, Louis P, Fava F, Franciosi E, Scholz M, Tuohy KM, Lindsay JO, Irving PM et al (2017) A diet low in FODMAPs reduces symptoms in patients with irritable bowel syndrome and a probiotic restores bifidobacterium species: a randomized controlled trial. Gastroenterology 153:936–947

    Article  CAS  PubMed  Google Scholar 

  • Stojanovska V, McQuade RM, Fraser S, Prakash M, Gondalia S, Stavely R, Palombo E, Apostolopoulos V, Sakkal S, Nurgali K (2018) Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. PLoS One 13:e0198359

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stollman N, Raskin JB (2004) Diverticular disease of the colon. Lancet Lond. Engl. 363:631–639

    Article  Google Scholar 

  • Strandwitz P (2018) Neurotransmitter modulation by the gut microbiota. Brain Res 1693:128–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strober W, Fuss I, Mannon P (2007) The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 117:514–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su T, Liu R, Lee A, Long Y, Du L, Lai S, Chen X, Wang L, Si J, Owyang C et al (2018) Altered intestinal microbiota with increased abundance of prevotella is associated with high risk of diarrhea-predominant irritable bowel syndrome. Gastroenterol. Res. Pract. 2018:6961783

    PubMed  PubMed Central  Google Scholar 

  • Sudo N (2012) Role of microbiome in regulating the HPA axis and its relevance to allergy. Chem Immunol Allergy 98:163–175

    Article  CAS  PubMed  Google Scholar 

  • Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu X-N, Kubo C, Koga Y (2004) Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 558:263–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki H, Moayyedi P (2013) Helicobacter pylori infection in functional dyspepsia. Nat. Rev. Gastroenterol. Hepatol. 10:168–174

    Article  PubMed  Google Scholar 

  • Szajewska H, Dryl R (2016) Probiotics for the management of infantile colic. J Pediatr Gastroenterol Nutr 63(Suppl 1):S22–S24

    PubMed  Google Scholar 

  • Takagi A, Yanagi H, Ozawa H, Uemura N, Nakajima S, Inoue K, Kawai T, Ohtsu T, Koga Y (2016) Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-associated dyspepsia: a multicenter randomized double-blind controlled trial. Gastroenterol. Res. Pract. 2016:7490452

    Article  PubMed  PubMed Central  Google Scholar 

  • Talley NJ (2017) Functional dyspepsia: advances in diagnosis and therapy. Gut Liver 11:349–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talley NJ, Ford AC (2016) Functional dyspepsia. N Engl J Med 374:896

    Article  PubMed  Google Scholar 

  • Tan KSW (2008) New insights on classification, identification, and clinical relevance of Blastocystis spp. Clin Microbiol Rev 21:639–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan VPY, Liu KSH, Lam FYF, Hung IFN, Yuen MF, Leung WK (2017) Randomised clinical trial: rifaximin versus placebo for the treatment of functional dyspepsia. Aliment Pharmacol Ther 45:767–776

    Article  CAS  PubMed  Google Scholar 

  • Tana C, Umesaki Y, Imaoka A, Handa T, Kanazawa M, Fukudo S (2010) Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 22(512–519):e114–e115

    Google Scholar 

  • Tap J, Derrien M, Törnblom H, Brazeilles R, Cools-Portier S, Doré J, Störsrud S, Le Nevé B, Öhman L, Simrén M (2017) Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome. Gastroenterology 152:111–123.e8

    Article  PubMed  Google Scholar 

  • Treem WR, Ahsan N, Kastoff G, Hyams JS (1996) Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. J Pediatr Gastroenterol Nutr 23:280–286

    Article  CAS  PubMed  Google Scholar 

  • Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, Verna EC, Volta U, Alaedini A (2016) Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut 65:1930–1937

    Article  CAS  PubMed  Google Scholar 

  • Valencia PM, Richard M, Brock J, Boglioli E (2017) The human microbiome: opportunity or hype? Nat. Rev. Drug Discov. 16:823–824

    Article  CAS  PubMed  Google Scholar 

  • Van de Wiele T, Van Praet JT, Marzorati M, Drennan MB, Elewaut D (2016) How the microbiota shapes rheumatic diseases. Nat Rev Rheumatol 12:398–411

    Article  PubMed  CAS  Google Scholar 

  • Vandeputte D, Falony G, Vieira-Silva S, Tito RY, Joossens M, Raes J (2016) Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65:57–62

    Article  CAS  PubMed  Google Scholar 

  • Verdú EF, Bercik P, Verma-Gandhu M, Huang X-X, Blennerhassett P, Jackson W, Mao Y, Wang L, Rochat F, Collins SM (2006) Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 55:182–190

    Article  PubMed  PubMed Central  Google Scholar 

  • Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ et al (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342:971–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vivinus-Nébot M, Frin-Mathy G, Bzioueche H, Dainese R, Bernard G, Anty R, Filippi J, Saint-Paul MC, Tulic MK, Verhasselt V et al (2014) Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut 63:744–752

    Article  PubMed  CAS  Google Scholar 

  • Wallace KL, Zheng L-B, Kanazawa Y, Shih DQ (2014) Immunopathology of inflammatory bowel disease. World J Gastroenterol 20:6–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H-B, Wang P-Y, Wang X, Wan Y-L, Liu Y-C (2012) Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein claudin-1 transcription. Dig Dis Sci 57:3126–3135

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Christophersen CT, Sorich MJ, Gerber JP, Angley MT, Conlon MA (2013) Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol Autism 4:42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wensaas K-A, Langeland N, Hanevik K, Mørch K, Eide GE, Rortveit G (2012) Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study. Gut 61:214–219

    Article  PubMed  Google Scholar 

  • Whelan K, Martin LD, Staudacher HM, Lomer MCE (2018) The low FODMAP diet in the management of irritable bowel syndrome: an evidence-based review of FODMAP restriction, reintroduction and personalisation in clinical practice. J. Hum Nutr Diet 31:239–255

    Article  CAS  PubMed  Google Scholar 

  • White RJ (2009) Wound infection-associated pain. J. Wound Care 18:245–249

    Article  CAS  PubMed  Google Scholar 

  • Wolf AJ, Underhill DM (2018) Peptidoglycan recognition by the innate immune system. Nat Rev Immunol 18:243–254

    Article  CAS  PubMed  Google Scholar 

  • Wrzosek L, Miquel S, Noordine M-L, Bouet S, Chevalier-Curt MJ, Robert V, Philippe C, Bridonneau C, Cherbuy C, Robbe-Masselot C et al (2013) Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol 11:61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu Z-Z, Kim YH, Bang S, Zhang Y, Berta T, Wang F, Oh SB, Ji R-R (2015) Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade. Nat Med 21:1326–1331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu D, Chen VL, Steiner CA, Berinstein JA, Eswaran S, Waljee AK, Higgins PDR, Owyang C (2019) Efficacy of fecal microbiota transplantation in irritable bowel syndrome: a systematic review and meta-analysis. Am. J. Gastroenterol 114:1043–1050

    Article  PubMed  PubMed Central  Google Scholar 

  • Yılmaz İ, Dolar ME, Özpınar H (2019) Effect of administering kefir on the changes in fecal microbiota and symptoms of inflammatory bowel disease: a randomized controlled trial. Turk J Gastroenterol 30:242–253

    Article  PubMed  Google Scholar 

  • Yoon H, Lee DH, Lee Y-H, Jeong J-C, Lee ST, Choi M-G, Jeon SW, Shim K-N, Baik GH, Kim JG et al (2018) Efficacy and safety of UI05MSP015CT in functional dyspepsia: a randomized, controlled trial. Gut Liver 12:516–522

    Article  PubMed  PubMed Central  Google Scholar 

  • Youn YH, Kim HC, Lim HC, Park JJ, Kim J-H, Park H (2016) Long-term clinical course of post-infectious irritable bowel syndrome after shigellosis: a 10-year follow-up study. J Neurogastroenterol Motil 22:490–496

    Article  PubMed  PubMed Central  Google Scholar 

  • Zahedi MJ, Behrouz V, Azimi M (2018) Low fermentable oligo-di-mono-saccharides and polyols diet versus general dietary advice in patients with diarrhea-predominant irritable bowel syndrome: a randomized controlled trial. J Gastroenterol Hepatol 33:1192–1199

    Article  CAS  PubMed  Google Scholar 

  • Zanini B, Ricci C, Bandera F, Caselani F, Magni A, Laronga AM, Lanzini A, San Felice del Benaco Study Investigators (2012) Incidence of post-infectious irritable bowel syndrome and functional intestinal disorders following a water-borne viral gastroenteritis outbreak. Am. J. Gastroenterol. 107:891–899

    Article  PubMed  Google Scholar 

  • Zhan Y, Zhan Y-A, Dai S-X (2018) Is a low FODMAP diet beneficial for patients with inflammatory bowel disease? A meta-analysis and systematic review. Clin Nutr Edinb Scotl 37:123–129

    Article  Google Scholar 

  • Zhuang X, Xiong L, Li L, Li M, Chen M (2017) Alterations of gut microbiota in patients with irritable bowel syndrome: a systematic review and meta-analysis. J Gastroenterol Hepatol 32:28–38

    Article  PubMed  Google Scholar 

  • Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori-Bachash M, Bashiardes S, Kotler E, Zur M, Regev-Lehavi D, Brik RB-Z et al (2018) Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174:1388–1405.e21

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Manon Defaye and Sandie Gervason contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Inflammation Research Network, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada

    Manon Defaye & Christophe Altier

  2. GREENTECH SA, Saint-Beauzire, France

    Sandie Gervason, Jean-Yves Berthon & Edith Filaire

  3. Université Clermont Auvergne, INSERM U1107, NeuroDol, CRHN Auvergne, 28 place Henri Dunant, BP 38, 63001, Clermont-Ferrand, France

    Sandie Gervason, Denis Ardid & Frédéric Antonio Carvalho

  4. Université Clermont Auvergne, INRA, Unité de Nutrition Humaine ECREIN, CRNH Auvergne, 63000, Clermont-Ferrand, France

    Edith Filaire

Authors
  1. Manon Defaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandie Gervason
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christophe Altier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jean-Yves Berthon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Denis Ardid
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Edith Filaire
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Frédéric Antonio Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frédéric Antonio Carvalho.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Defaye, M., Gervason, S., Altier, C. et al. Microbiota: a novel regulator of pain. J Neural Transm 127, 445–465 (2020). https://doi.org/10.1007/s00702-019-02083-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-019-02083-z

Keywords

Search

Navigation