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P841 Small intestinal bacterial overgrowth in patients with Crohn’s disease is not only associated with a more severe disease, but is also marked by dramatic changes in the gut microbiome

Y. Kulygina1, M. Osipenko1, M. Skalinskaya2, T. Alikina3, M. Kabilov3, V. Lukinov4, S. Sitkin*2,5

1Novosibirsk State Medical University, Department of Internal Diseases, Novosibirsk, Russian Federation, 2North-Western State Medical University named after I.I. Mechnikov, Department of Internal Diseases, Gastroenterology and Dietetics named after S.M. Ryss, St. Petersburg, Russian Federation, 3Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russian Federation, 4Institute of Computational Mathematics and Mathematical Geophysics SB RAS, Novosibirsk, Russian Federation, 5State Research Institute of Highly Pure Biopreparations of FMBA, Department of Microbiology, St. Petersburg, Russian Federation

Background

The main mechanisms that protect against small intestinal bacterial overgrowth (SIBO) are compromised in Crohn’s disease (CD). Therefore, SIBO is a relatively common finding in patients with CD with a reported frequency of 17% to 62%. SIBO represents a clinically relevant event in CD that may affect the symptoms and outcomes. Gut microbiota dysbiosis is strongly associated with CD, but effect of SIBO on the colonic microbiome is not so clear. The aim of this study was to characterise the faecal microbiota composition in adult patients with CD, with or without SIBO.

Methods

A pilot comparative study among CD patients with (n = 36) and without (n = 35) SIBO was conducted, with a focus on differences in the gut microbiome. A lactulose hydrogen breath test (LHBT) was used to determine the presence of SIBO. V3-V4 16S rRNA deep amplicon sequencing on the Illumina MiSeq platform with Reagent Kit v3 (600 cycles) was used to analyse faecal microbiota.

Results

51% of patients with CD had an abnormal LHBT, indicating the presence of SIBO. LHBT results were not associated with gender, age, body height, disease location, duration of the disease, treatment difference, presence of steroid dependency or steroid resistance.

CD patients with SIBO, when compared with those without SIBO, were characterised by a significant decrease in body weight within the last 3 months prior to the study, with an average loss in body mass of 2.5 kg (p < 0.001).

Patients with the higher Crohn’s disease Activity Index (CDAI) scores ( ≥300) were more likely to have SIBO, when compared with those with CDAI < 300 (81% vs. 32%; p < 0.001). SIBO was significantly more common in patients with structuring or penetrating (B2/B3) behaviour than in patients with non‐stricturing, non‐penetrating disease (B1) (83% vs. 27%; p < 0.001). Patients with SIBO were more likely to have moderate or severe abdominal pain (64% vs. 25%; p = 0.007), bloating (86% vs. 31%; p < 0.001), flatulence (75% vs. 6%; p < 0.001) and fatigue (81% vs. 54%; p = 0.023), when compared with patients without SIBO. Some potentially harmful microbes were more abundant in CD patients with SIBO such as those belonging to the Fusobacteria, Proteobacteria, Erysipelotrichaceae, Escherichia/Shigella. Bifidobacteriales and Lactobacillales, generally considered to be beneficial, were lowered in patients with SIBO. Some bacteria, that may play a dual role (protective or detrimental) were increased (Bacteroidetes, Lachnospiraceae, Verrucomicrobiaceae, Akkermansia, Blautia, Dorea), while others (Enterococcaceae) were decreased in SIBO.

Conclusion

SIBO in patients with CD was associated not only with a more severe disease but also with significant changes in the gut microbiome that may worsen the symptoms and the course of the disease.