Skip to main content
Erschienen in: Journal of Gastroenterology 12/2020

16.10.2020 | Original Article—Alimentary Tract

The microbiome can predict mucosal healing in small intestine in patients with Crohn’s disease

verfasst von: Shun Hattori, Masanao Nakamura, Takeshi Yamamura, Keiko Maeda, Tsunaki Sawada, Yasuyuki Mizutani, Kenta Yamamoto, Takuya Ishikawa, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Yoshiki Hirooka, Mitsuhiro Fujishiro

Erschienen in: Journal of Gastroenterology | Ausgabe 12/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Mucosal healing is the main treatment goal for Crohn’s disease. In this situation, some patients have difficulty with endoscopic evaluation of the entire small intestine. Crohn’s disease is closely associated with the gut microbiota, but the relationship between the microbiome and disease activity in the small intestine remains unclear. We examined the association between the microbiome and endoscopic findings in the small intestine and determined whether the microbiome can predict mucosal healing.

Methods

The patients with Crohn’s disease who were scheduled for capsule or balloon-assisted endoscopy were included in this prospective study. Patients whose entire small intestine was evaluated were divided into two groups based on ulcerative findings. The microbiomes in the fecal samples were analyzed using 16S rRNA sequencing.

Results

The 38 enrolled patients were divided into the ulcer group (24) and mucosal healing group (14). The ulcer group exhibited lower α diversity. Six genera, namely Faecalibacterium (P = 0.008), Lachnospira (P = 0.009), Paraprevotella (P = 0.01), Dialister (P = 0.012), Streptococcus (P = 0.025), and Clostridium (P = 0.028) were enriched in the mucosal healing group. A predictive score for mucosal healing was defined using these six genera. The area under the curve was 0.795 and the sensitivity and specificity for predicting mucosal healing were 0.643 and 0.917, respectively.

Conclusions

Fecal microbiome is corelated with disease activity in the entire small intestine in Crohn’s disease patients. The predictive score proposed by microbiota characteristics was a potential biomarker for mucosal healing in the small intestine.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Torres J, Mehandru S, Colombel J, et al. Crohn’s disease. Lancet. 2016;6736:1–15. Torres J, Mehandru S, Colombel J, et al. Crohn’s disease. Lancet. 2016;6736:1–15.
2.
Zurück zum Zitat Peyrin-Biroulet L, Colombel J-F, et al. The natural history of adult Crohn’s disease in population-based cohorts. Am J Gastroenterol. 2010;105:289–97.PubMed Peyrin-Biroulet L, Colombel J-F, et al. The natural history of adult Crohn’s disease in population-based cohorts. Am J Gastroenterol. 2010;105:289–97.PubMed
3.
Zurück zum Zitat Pariente B, Cosnes J, Danese S, et al. Development of the Crohn’s disease digestive damage score, the Lémann score. Inflamm Bowel Dis. 2011;17:1415–22.PubMed Pariente B, Cosnes J, Danese S, et al. Development of the Crohn’s disease digestive damage score, the Lémann score. Inflamm Bowel Dis. 2011;17:1415–22.PubMed
4.
Zurück zum Zitat Modigliani R, Mary J-Y, Simon J-F, et al. Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Gastroenterology. 2011;98:811–8. Modigliani R, Mary J-Y, Simon J-F, et al. Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Gastroenterology. 2011;98:811–8.
5.
Zurück zum Zitat Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–8.PubMed Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–8.PubMed
6.
Zurück zum Zitat Schnitzler F, Fidder H, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–301.PubMed Schnitzler F, Fidder H, Ferrante M, et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn’s disease. Inflamm Bowel Dis. 2009;15:1295–301.PubMed
7.
Zurück zum Zitat Annese V, Daperno M, Rutter MD, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohn’s Colitis. 2013;7:982–1018. Annese V, Daperno M, Rutter MD, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohn’s Colitis. 2013;7:982–1018.
9.
Zurück zum Zitat Melmed GY, Dubinsky MC, Rubin DT, et al. Utility of video capsule endoscopy for longitudinal monitoring of Crohn’s disease activity in the small bowel: a prospective study. Gastrointest Endosc. 2018;88:947–55.PubMed Melmed GY, Dubinsky MC, Rubin DT, et al. Utility of video capsule endoscopy for longitudinal monitoring of Crohn’s disease activity in the small bowel: a prospective study. Gastrointest Endosc. 2018;88:947–55.PubMed
10.
Zurück zum Zitat Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases. Clin Gastroenterol Hepatol. 2004;2:1010–6.PubMed Yamamoto H, Kita H, Sunada K, et al. Clinical outcomes of double-balloon endoscopy for the diagnosis and treatment of small-intestinal diseases. Clin Gastroenterol Hepatol. 2004;2:1010–6.PubMed
11.
Zurück zum Zitat Zepeda-Gómez S, Barreto-Zuñiga R, Ponce-De-León S, et al. Risk of hyperamylasemia and acute pancreatitis after double-balloon enteroscopy: a prospective study. Endoscopy. 2011;43:766–70.PubMed Zepeda-Gómez S, Barreto-Zuñiga R, Ponce-De-León S, et al. Risk of hyperamylasemia and acute pancreatitis after double-balloon enteroscopy: a prospective study. Endoscopy. 2011;43:766–70.PubMed
12.
Zurück zum Zitat Mensink P, Haringsma J, Kucharzik TF, et al. Complications of double balloon enteroscopy: a multicenter survey. Endoscopy. 2007;39:613–5.PubMed Mensink P, Haringsma J, Kucharzik TF, et al. Complications of double balloon enteroscopy: a multicenter survey. Endoscopy. 2007;39:613–5.PubMed
13.
Zurück zum Zitat Langhorst J, Elsenbruch S, Koelzer J, et al. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol. 2008;103:162–9.PubMed Langhorst J, Elsenbruch S, Koelzer J, et al. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. Am J Gastroenterol. 2008;103:162–9.PubMed
14.
Zurück zum Zitat Hold GL, Smith M, Grange C, et al. Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? World J Gastroenterol. 2014;20:1192–210.PubMedPubMedCentral Hold GL, Smith M, Grange C, et al. Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? World J Gastroenterol. 2014;20:1192–210.PubMedPubMedCentral
15.
Zurück zum Zitat Wills ES, Jonkers DMAE, Savelkoul PH, et al. Fecal microbial composition of ulcerative colitis and Crohn’s disease patients in remission and subsequent exacerbation. PLoS ONE. 2014;9:1–10. Wills ES, Jonkers DMAE, Savelkoul PH, et al. Fecal microbial composition of ulcerative colitis and Crohn’s disease patients in remission and subsequent exacerbation. PLoS ONE. 2014;9:1–10.
16.
Zurück zum Zitat Swidsinski A, Loening-Baucke V, Vaneechoutte M, et al. Active Crohnʼs disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis. 2008;14:147–61.PubMed Swidsinski A, Loening-Baucke V, Vaneechoutte M, et al. Active Crohnʼs disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis. 2008;14:147–61.PubMed
17.
Zurück zum Zitat Xavier RJ. Microbiota as therapeutic targets. Dig Dis. 2016;34:558–65.PubMed Xavier RJ. Microbiota as therapeutic targets. Dig Dis. 2016;34:558–65.PubMed
18.
Zurück zum Zitat Joossens M, Huys G, Cnockaert M, et al. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut. 2011;60:631–7.PubMed Joossens M, Huys G, Cnockaert M, et al. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut. 2011;60:631–7.PubMed
19.
Zurück zum Zitat Willing BP, Dicksved J, Halfvarson J, et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology. 2010;139:1844–54.PubMed Willing BP, Dicksved J, Halfvarson J, et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology. 2010;139:1844–54.PubMed
20.
Zurück zum Zitat Willing B, Halfvarson J, Dicksved J, et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn’s disease. Inflamm Bowel Dis. 2009;15:653–60.PubMed Willing B, Halfvarson J, Dicksved J, et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn’s disease. Inflamm Bowel Dis. 2009;15:653–60.PubMed
21.
Zurück zum Zitat Vandeputte D, Falony G, Vieira-Silva S, et al. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut. 2016;65:57–62.PubMed Vandeputte D, Falony G, Vieira-Silva S, et al. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut. 2016;65:57–62.PubMed
22.
Zurück zum Zitat Nishimoto Y, Mizutani S, Nakajima T, et al. High stability of faecal microbiome composition in guanidine thiocyanate solution at room temperature and robustness during colonoscopy. Gut. 2016;65:1574–5.PubMed Nishimoto Y, Mizutani S, Nakajima T, et al. High stability of faecal microbiome composition in guanidine thiocyanate solution at room temperature and robustness during colonoscopy. Gut. 2016;65:1574–5.PubMed
23.
Zurück zum Zitat DeSantis TZ, Hugenholtz P, Larsen N, et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006;72:5069–72.PubMedPubMedCentral DeSantis TZ, Hugenholtz P, Larsen N, et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol. 2006;72:5069–72.PubMedPubMedCentral
24.
Zurück zum Zitat Navas-Molina JA, Peralta-Sánchez JM, González A, et al. Advancing our understanding of the human microbiome using QIIME. Methods Enzymol. 2013;531:371–444.PubMedPubMedCentral Navas-Molina JA, Peralta-Sánchez JM, González A, et al. Advancing our understanding of the human microbiome using QIIME. Methods Enzymol. 2013;531:371–444.PubMedPubMedCentral
25.
26.
Zurück zum Zitat Prosberg M, Bendtsen F, Vind I, et al. The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis. Scand J Gastroenterol. 2016;51:1407–15.PubMed Prosberg M, Bendtsen F, Vind I, et al. The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis. Scand J Gastroenterol. 2016;51:1407–15.PubMed
27.
Zurück zum Zitat Pascal V, Pozuelo M, Borruel N, et al. A microbial signature for Crohn’s disease. Gut. 2017;66:813–22.PubMed Pascal V, Pozuelo M, Borruel N, et al. A microbial signature for Crohn’s disease. Gut. 2017;66:813–22.PubMed
28.
Zurück zum Zitat Sommer F, Rühlemann MC, Bang C, et al. Microbiomarkers in inflammatory bowel diseases: caveats come with caviar. Gut. 2017;66:1734–8.PubMed Sommer F, Rühlemann MC, Bang C, et al. Microbiomarkers in inflammatory bowel diseases: caveats come with caviar. Gut. 2017;66:1734–8.PubMed
29.
Zurück zum Zitat Furet JP, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.PubMedPubMedCentral Furet JP, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.PubMedPubMedCentral
30.
Zurück zum Zitat Graessler J, Qin Y, Zhong H, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13:514–22.PubMed Graessler J, Qin Y, Zhong H, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13:514–22.PubMed
31.
Zurück zum Zitat Balamurugan R, Rajendiran E, George S, et al. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol. 2008;23:1298–303.PubMed Balamurugan R, Rajendiran E, George S, et al. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol. 2008;23:1298–303.PubMed
32.
Zurück zum Zitat Lopez-Siles M, Martinez-Medina M, Surís-Valls R, et al. Changes in the abundance of faecalibacterium prausnitzii phylogroups i and ii in the intestinal mucosa of inflammatory bowel disease and patients with colorectal cancer. Inflamm Bowel Dis. 2016;22:28–41.PubMed Lopez-Siles M, Martinez-Medina M, Surís-Valls R, et al. Changes in the abundance of faecalibacterium prausnitzii phylogroups i and ii in the intestinal mucosa of inflammatory bowel disease and patients with colorectal cancer. Inflamm Bowel Dis. 2016;22:28–41.PubMed
33.
Zurück zum Zitat Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105:16731–6.PubMedPubMedCentral Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105:16731–6.PubMedPubMedCentral
34.
Zurück zum Zitat Sokol H, Seksik P, Furet JP, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15:1183–9.PubMed Sokol H, Seksik P, Furet JP, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15:1183–9.PubMed
35.
Zurück zum Zitat Machiels K, Joossens M, Sabino J, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63:1275–83.PubMed Machiels K, Joossens M, Sabino J, et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63:1275–83.PubMed
36.
Zurück zum Zitat Lopez-Siles M, Martinez-Medina M, Busquets D, et al. Mucosa-associated Faecalibacterium prausnitzii and Escherichia coli co-abundance can distinguish Irritable Bowel Syndrome and Inflammatory Bowel Disease phenotypes. Int J Med Microbiol. 2014;304:464–75.PubMed Lopez-Siles M, Martinez-Medina M, Busquets D, et al. Mucosa-associated Faecalibacterium prausnitzii and Escherichia coli co-abundance can distinguish Irritable Bowel Syndrome and Inflammatory Bowel Disease phenotypes. Int J Med Microbiol. 2014;304:464–75.PubMed
37.
Zurück zum Zitat Carlsson AH, Yakymenko O, Olivier I, et al. Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis. Scand J Gastroenterol. 2013;48:1136–44.PubMed Carlsson AH, Yakymenko O, Olivier I, et al. Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis. Scand J Gastroenterol. 2013;48:1136–44.PubMed
38.
Zurück zum Zitat Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41.PubMed Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41.PubMed
39.
40.
Zurück zum Zitat Erickson AR, Cantarel BL, Lamendella R, et al. Integrated metagenomics / metaproteomics reveals human host-microbiota signatures of Crohn’s disease. PLoS ONE. 2012;7:e49138.PubMedPubMedCentral Erickson AR, Cantarel BL, Lamendella R, et al. Integrated metagenomics / metaproteomics reveals human host-microbiota signatures of Crohn’s disease. PLoS ONE. 2012;7:e49138.PubMedPubMedCentral
41.
Zurück zum Zitat Imhann F, Bonder MJ, Vich Vila A, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–8.PubMed Imhann F, Bonder MJ, Vich Vila A, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–8.PubMed
42.
Zurück zum Zitat Estevinho MM, Rocha C, Correia L, et al. Features of fecal and colon microbiomes associate with responses to biologic therapies for inflammatory bowel diseases: a systematic review. Clin Gastroenterol Hepatol. 2020;18:1054–69.PubMed Estevinho MM, Rocha C, Correia L, et al. Features of fecal and colon microbiomes associate with responses to biologic therapies for inflammatory bowel diseases: a systematic review. Clin Gastroenterol Hepatol. 2020;18:1054–69.PubMed
Metadaten
Titel
The microbiome can predict mucosal healing in small intestine in patients with Crohn’s disease
verfasst von
Shun Hattori
Masanao Nakamura
Takeshi Yamamura
Keiko Maeda
Tsunaki Sawada
Yasuyuki Mizutani
Kenta Yamamoto
Takuya Ishikawa
Kazuhiro Furukawa
Eizaburo Ohno
Takashi Honda
Hiroki Kawashima
Masatoshi Ishigami
Yoshiki Hirooka
Mitsuhiro Fujishiro
Publikationsdatum
16.10.2020
Verlag
Springer Singapore
Erschienen in
Journal of Gastroenterology / Ausgabe 12/2020
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-020-01728-1

Weitere Artikel der Ausgabe 12/2020

Journal of Gastroenterology 12/2020 Zur Ausgabe

Original Article—Liver, Pancreas, and Biliary Tract

Durable response without recurrence to Tolvaptan improves long-term survival

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.