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.
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.
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.
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.
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Positive predictive value
Negative predictive value
Under the curve
Linear discriminant analysis Effect Size
Principal Coordinate Analysis
Torres J, Mehandru S, Colombel J, et al. Crohn’s disease. Lancet. 2016;6736:1–15.
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.
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.
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.
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.
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.
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.
Takenaka K, Fujii T, Suzuki K, et al. Small bowel healing detected by endoscopy in patients with Crohn’s disease after treatment with antibodies against tumor necrosis factor. Clin Gastroenterol Hepatrol. 2019. https://doi.org/10.1016/j.cgh.2019.08.024.
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.
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.
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.
Mensink P, Haringsma J, Kucharzik TF, et al. Complications of double balloon enteroscopy: a multicenter survey. Endoscopy. 2007;39:613–5.
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.
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.
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.
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.
Xavier RJ. Microbiota as therapeutic targets. Dig Dis. 2016;34:558–65.
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.
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.
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.
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.
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.
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.
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.
Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.
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.
Pascal V, Pozuelo M, Borruel N, et al. A microbial signature for Crohn’s disease. Gut. 2017;66:813–22.
Sommer F, Rühlemann MC, Bang C, et al. Microbiomarkers in inflammatory bowel diseases: caveats come with caviar. Gut. 2017;66:1734–8.
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.
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.
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.
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.
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.
Sokol H, Seksik P, Furet JP, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009;15:1183–9.
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.
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.
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.
Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41.
Gevers D. The treat ment-naïve microbiome in new-onset Crohn’ s disease. Cell Host Microbe. 2014;15:382–92.
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.
Imhann F, Bonder MJ, Vich Vila A, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–8.
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.
We received no financial support for this research. We thank Ms. Akina Ooishi at the Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine for technical assistance in DNA isolation and 16S rRNA gene sequencing.
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Hattori, S., Nakamura, M., Yamamura, T. et al. The microbiome can predict mucosal healing in small intestine in patients with Crohn’s disease. J Gastroenterol 55, 1138–1149 (2020). https://doi.org/10.1007/s00535-020-01728-1
- Crohn’s disease
- Gut microbiota
- Mucosal healing
- Small intestine