肠道菌群对脑-肠轴和功能性消化不良的影响
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摘要
肠道菌群是多种消化系统和神经系统疾病的致病因素。研究表明肠道菌群与脑-肠轴具有双向联系,对神经系统发育和功能、胃肠道功能等具有调节作用。功能性消化不良(FD)是常见的功能性胃肠病,其发病机制尚未完全阐明,近年研究表明肠道菌群在FD发病中起有重要作用。本文就肠道菌群对脑-肠轴和FD的影响作一综述。
Intestinal microbiota can act as a pathogenic factor for a variety of diseases of digestive system and nervous system. Studies have revealed the bidirectional connection between intestinal microbiota and brain-gut axis. And it is illustrated that the intestinal microbiota plays a significant role in the regulation of nervous system as well as gastrointestinal function. Functional dyspepsia (FD) is a common functional gastrointestinal disorder,and the pathogenesis has not yet been fully elucidated. In recent years,studies have indicated that intestinal microbiota may influence the genesis of FD.This article reviewed the effects of intestinal microbiota on brain-gut axis and FD.
Intestinal microbiota can act as a pathogenic factor for a variety of diseases of digestive system and nervous system. Studies have revealed the bidirectional connection between intestinal microbiota and brain-gut axis. And it is illustrated that the intestinal microbiota plays a significant role in the regulation of nervous system as well as gastrointestinal function. Functional dyspepsia (FD) is a common functional gastrointestinal disorder,and the pathogenesis has not yet been fully elucidated. In recent years,studies have indicated that intestinal microbiota may influence the genesis of FD.This article reviewed the effects of intestinal microbiota on brain-gut axis and FD.
引文
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2 Nicholson JK,Holmes E,Kinross J,et al.Host-gut microbiota metabolic interactions[J].Science,2012,336(6086):1262-1267.
3 Mayer EA,Tillisch K,Gupta A.Gut/brain axis and the microbiota[J].J Clin Invest,2015,125(3):926-938.
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6 Diaz Heijtz R,Wang S,Anuar F,et al.Normal gut microbiota modulates brain development and behavior[J].Proc Natl Acad Sci U S A,2011,108(7):3047-3052.
7 Quigley EMM.Microbiota-Brain-Gut Axis and Neurodegenerative Diseases[J].Curr Neurol Neurosci Rep,2017,17(12):94.
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15 Agrawal A,Houghton LA,Morris J,et al.Clinical trial:the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation[J].Aliment Pharmacol Ther,2009,29(1):104-114.
16 Sampson TR,Debelius JW,Thron T,et al.Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease[J].Cell,2016,167(6):1469-1480.e12.
17 Grasa L,Abecia L,Forcén R,et al.Antibiotic-Induced Depletion of Murine Microbiota Induces Mild Inflammation and Changes in Toll-Like Receptor Patterns and Intestinal Motility[J].Microb Ecol,2015,70(3):835-848.
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23 Enck P,Azpiroz F,Boeckxstaens G,et al.Functional dyspepsia[J].Nat Rev Dis Primers,2017,3:17081.
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25 Suzuki H,Moayyedi P.Helicobacter pylori infection in functional dyspepsia[J].Nat Rev Gastroenterol Hepatol,2013,10(3):168-174.
26 Futagami S,Itoh T,Sakamoto C.Systematic review with meta-analysis:post-infectious functional dyspepsia[J].Aliment Pharmacol Ther,2015,41(2):177-188.
27 Zhong L,Shanahan ER,Raj A,et al.Dyspepsia and the microbiome:time to focus on the small intestine[J].Gut,2017,66(6):1168-1169.
28 Kim N,Yun M,Oh YJ,et al.Mind-altering with the gut:Modulation of the gut-brain axis with probiotics[J].JMicrobiol,2018,56(3):172-182.
29 Gomi A,Yamaji K,Watanabe O,et al.Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults:A double-blind,randomized,placebo-controlled study[J].J Dairy Sci,2018,101(6):4830-4841.
30 Stilling RM,Ryan FJ,Hoban AE,et al.Microbes&neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala[J].Brain Behav Immun,2015,50:209-220.
31 Van Oudenhove L,Crowell MD,Drossman DA,et al.Biopsychosocial Aspects of Functional Gastrointestinal Disorders[J].Gastroenterology,2016.pii:S0016-5085(16)00218-3.
32 Zeng F,Qin W,Yang Y,et al.Regional brain structural abnormality in meal-related functional dyspepsia patients:a voxel-based morphometry study[J].PLo S One,2013,8(7):e68383.
33 Fan K,Talley NJ.Functional dyspepsia and duodenal eosinophilia:A new model[J].J Dig Dis,2017,18(12):667-677.
34 Jebbink RJ,van Berge-Henegouwen GP,Akkermans LM,et al.Antroduodenal manometry:24-hour ambulatory monitoring versus short-term stationary manometry in patients with functional dyspepsia[J].Eur J Gastroenterol Hepatol,1995,7(2):109-116.
35 Ly HG,Ceccarini J,Weltens N,et al.Increased cerebral cannabinoid-1 receptor availability is a stable feature of functional dyspepsia:a[F]MK-9470 PET study[J].Psychother Psychosom,2015,84(3):149-158.
36 Simrén M,T9rnblom H,Palsson OS,et al.Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders:consistent findings from five different patient cohorts[J].Gut,2018,67(2):255-262.
37 Hammer J,Führer M,Pipal L,et al.Hypersensitivity for capsaicin in patients with functional dyspepsia[J].Neurogastroenterol Motil,2008,20(2):125-133.
38 Walker MM,Talley NJ.The Role of Duodenal Inflammation in Functional Dyspepsia[J].J Clin Gastroenterol,2017,51(1):12-18.
2 Nicholson JK,Holmes E,Kinross J,et al.Host-gut microbiota metabolic interactions[J].Science,2012,336(6086):1262-1267.
3 Mayer EA,Tillisch K,Gupta A.Gut/brain axis and the microbiota[J].J Clin Invest,2015,125(3):926-938.
4 Cenit MC,Sanz Y,Codo1er-Franch P.Influence of gut microbiota on neuropsychiatric disorders[J].World JGastroenterol,2017,23(30):5486-5498.
5 Collins J,Borojevic R,Verdu EF,et al.Intestinal microbiota influence the early postnatal development of the enteric nervous system[J].Neurogastroenterol Motil,2014,26(1):98-107.
6 Diaz Heijtz R,Wang S,Anuar F,et al.Normal gut microbiota modulates brain development and behavior[J].Proc Natl Acad Sci U S A,2011,108(7):3047-3052.
7 Quigley EMM.Microbiota-Brain-Gut Axis and Neurodegenerative Diseases[J].Curr Neurol Neurosci Rep,2017,17(12):94.
8 Obata Y,Pachnis V.The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System[J].Gastroenterology,2016,151(5):836-844.
9 Foley KA,Mac Fabe DF,Vaz A,et al.Sexually dimorphic effects of prenatal exposure to propionic acid and lipopolysaccharide on social behavior in neonatal,adolescent,and adult rats:implications for autism spectrum disorders[J].Int J Dev Neurosci,2014,39:68-78.
10 Stilling RM,Dinan TG,Cryan JF.Microbial genes,brain&behaviour-epigenetic regulation of the gut-brain axis[J].Genes Brain Behav,2014,13(1):69-86.
11 Maynard CL,Elson CO,Hatton RD,et al.Reciprocal interactions of the intestinal microbiota and immune system[J].Nature,2012,489(7415):231-241.
12 Coccia M,Harrison OJ,Schiering C,et al.IL-1βmediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4(+)Th17cells[J].J Exp Med,2012,209(9):1595-1609.
13 Arpaia N,Campbell C,Fan X,et al.Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation[J].Nature,2013,504(7480):451-455.
14 Pan X,Gong D,Nguyen DN,et al.Early microbial colonization affects DNA methylation of genes related to intestinal immunity and metabolism in preterm pigs[J].DNARes,2018[Epub ahead of print].
15 Agrawal A,Houghton LA,Morris J,et al.Clinical trial:the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation[J].Aliment Pharmacol Ther,2009,29(1):104-114.
16 Sampson TR,Debelius JW,Thron T,et al.Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease[J].Cell,2016,167(6):1469-1480.e12.
17 Grasa L,Abecia L,Forcén R,et al.Antibiotic-Induced Depletion of Murine Microbiota Induces Mild Inflammation and Changes in Toll-Like Receptor Patterns and Intestinal Motility[J].Microb Ecol,2015,70(3):835-848.
18 VerdúEF,Bercik P,Verma-Gandhu M,et al.Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice[J].Gut,2006,55(2):182-190.
19 Crouzet L,Gaultier E,Del’Homme C,et al.The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota[J].Neurogastroenterol Motil,2013,25(4):e272-e282.
20 Botschuijver S,Roeselers G,Levin E,et al.Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats[J].Gastroenterology,2017,153(4):1026-1039.
21 Riba A,Olier M,Lacroix-LamandéS,et al.Paneth Cell Defects Induce Microbiota Dysbiosis in Mice and Promote Visceral Hypersensitivity[J].Gastroenterology,2017,153(6):1594-1606.e2.
22 Xu D,Gao J,Gillilland M 3rd,et al.Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats[J].Gastroenterology,2014,146(2):484-496.e4.
23 Enck P,Azpiroz F,Boeckxstaens G,et al.Functional dyspepsia[J].Nat Rev Dis Primers,2017,3:17081.
24 Igarashi M,Nakae H,Matsuoka T,et al.Alteration in the gastric microbiota and its restoration by probiotics in patients with functional dyspepsia[J].BMJ Open Gastroenterol,2017,4(1):e000144.
25 Suzuki H,Moayyedi P.Helicobacter pylori infection in functional dyspepsia[J].Nat Rev Gastroenterol Hepatol,2013,10(3):168-174.
26 Futagami S,Itoh T,Sakamoto C.Systematic review with meta-analysis:post-infectious functional dyspepsia[J].Aliment Pharmacol Ther,2015,41(2):177-188.
27 Zhong L,Shanahan ER,Raj A,et al.Dyspepsia and the microbiome:time to focus on the small intestine[J].Gut,2017,66(6):1168-1169.
28 Kim N,Yun M,Oh YJ,et al.Mind-altering with the gut:Modulation of the gut-brain axis with probiotics[J].JMicrobiol,2018,56(3):172-182.
29 Gomi A,Yamaji K,Watanabe O,et al.Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults:A double-blind,randomized,placebo-controlled study[J].J Dairy Sci,2018,101(6):4830-4841.
30 Stilling RM,Ryan FJ,Hoban AE,et al.Microbes&neurodevelopment--Absence of microbiota during early life increases activity-related transcriptional pathways in the amygdala[J].Brain Behav Immun,2015,50:209-220.
31 Van Oudenhove L,Crowell MD,Drossman DA,et al.Biopsychosocial Aspects of Functional Gastrointestinal Disorders[J].Gastroenterology,2016.pii:S0016-5085(16)00218-3.
32 Zeng F,Qin W,Yang Y,et al.Regional brain structural abnormality in meal-related functional dyspepsia patients:a voxel-based morphometry study[J].PLo S One,2013,8(7):e68383.
33 Fan K,Talley NJ.Functional dyspepsia and duodenal eosinophilia:A new model[J].J Dig Dis,2017,18(12):667-677.
34 Jebbink RJ,van Berge-Henegouwen GP,Akkermans LM,et al.Antroduodenal manometry:24-hour ambulatory monitoring versus short-term stationary manometry in patients with functional dyspepsia[J].Eur J Gastroenterol Hepatol,1995,7(2):109-116.
35 Ly HG,Ceccarini J,Weltens N,et al.Increased cerebral cannabinoid-1 receptor availability is a stable feature of functional dyspepsia:a[F]MK-9470 PET study[J].Psychother Psychosom,2015,84(3):149-158.
36 Simrén M,T9rnblom H,Palsson OS,et al.Visceral hypersensitivity is associated with GI symptom severity in functional GI disorders:consistent findings from five different patient cohorts[J].Gut,2018,67(2):255-262.
37 Hammer J,Führer M,Pipal L,et al.Hypersensitivity for capsaicin in patients with functional dyspepsia[J].Neurogastroenterol Motil,2008,20(2):125-133.
38 Walker MM,Talley NJ.The Role of Duodenal Inflammation in Functional Dyspepsia[J].J Clin Gastroenterol,2017,51(1):12-18.