Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease

Sonia Facchin, Nicola Vitulo, Matteo Calgaro, Andrea Buda, Chiara Romualdi, Daniel Pohl, Barbara Perini, Greta Lorenzon, Carla Marinelli, Renata D'Incà, Giacomo Carlo Sturniolo, Edoardo Vincenzo Savarino, Sonia Facchin, Nicola Vitulo, Matteo Calgaro, Andrea Buda, Chiara Romualdi, Daniel Pohl, Barbara Perini, Greta Lorenzon, Carla Marinelli, Renata D'Incà, Giacomo Carlo Sturniolo, Edoardo Vincenzo Savarino

Abstract

Background: Butyrate has shown anti-inflammatory and regenerative properties, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. We investigated the effect of a colonic-delivery formulation of butyrate on the fecal microbiota of patients with inflammatory bowel diseases (IBDs).

Methods: In this double-blind, placebo-controlled, pilot study, 49 IBD patients (n = 19 Crohn's disease, CD and n = 30 ulcerative colitis, UC) were randomized to oral administration of microencapsulated-sodium-butyrate (BLM) or placebo for 2 months, in addition to conventional therapy. Eighteen healthy volunteers (HVs) were recruited to provide a healthy microbiota model of the local people. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity and quality of life (QoL) were evaluated before and after treatment.

Key results: At baseline, HVs showed a different microbiota composition compared with IBD patients. Sodium-butyrate altered the gut microbiota of IBD patients by increasing bacteria able to produce SCFA in UC patients (Lachnospiraceae spp.) and the butyrogenic colonic bacteria in CD patients (Butyricicoccus). In UC patients, QoL was positively affected by treatment.

Conclusions and inferences: Sodium-butyrate supplementation increases the growth of bacteria able to produce SCFA with potentially anti-inflammatory action. The clinical impact of this finding requires further investigation.

Keywords: 16S metabarcoding; gut inflammation; inflammatory bowel disease; prebiotics; short-chain fatty acid.

Conflict of interest statement

The authors report no conflict of interest.

© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Graphic summary. Project study design: 18 healthy subjects and forty‐nine patients (21 on butyrose group and 28 on placebo group; 19 CD patients and 30 UC patients) were enrolled for this study. Pie charts show the microbial composition at phylum level in the different groups of samples
Figure 2
Figure 2
Box‐plot comparison of the alfa diversity calculated using Fisher metric between IBD and healthy group (A), timepoint T0 and T1 within the BLM group (B), and PBO group (C). Analysis performed with other distances confirms the same results (data not shown)
Figure 3
Figure 3
PERMANOVA tests if samples can be significantly separated accordingly to different variables (eg, treatment or type of disease). The figure shows the principal coordinate analysis considering the samples grouped according to (A) healthy and IBD status, (B) treatment (placebo and butyrose) at T0 = baseline and T1 = post‐treatment, (C) disease (UC and CD) undergoing BLM or PBO treatment at T0 and T1 timepoint, and (D) disease activity (1 indicates an active disease, while 0 a non‐active disease). The P‐value derived from the PERMANOVA test is reported for each comparison, and significant P‐value (<0.05) is indicated with a star
Figure 4
Figure 4
Barplot of the microbial composition at phylum level: average ASV abundance percentages of the samples stratified by treatment (butyrose, placebo, or control), disease (CD, UC, or control), and timepoint (T0 = baseline or T1 = post‐treatment)
Figure 5
Figure 5
sPLS‐DA analysis identified a subset of discriminant ASVs: for each ASV, a loading value that represents the discriminant power of that ASV in explaining differences between 2 examined conditions. The higher the absolute value, the bigger is the discriminative power. The loading value plots display the top 15 (panels A‐E) and top 6 (panel F) discriminant ASVs for each comparison. Percentages shown in the bars represent the mean relative abundances of each ASV in the considered conditions. The dark color and a light color of each bar represent the average relative abundance (in percentage) of an ASV in the considered comparison

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