Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome

Abstract

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS.

Figure 1

Unweighted UniFrac data redundancy analysis on the first time point samples constrained by (A) controls and IBS patients groups, and (B) constrained by the four groups of participants: controls (n = 66), IBS-C (n = 32), IBS-D (n = 54) and IBS-M (n = 27).

Figure 2. Higher relative abundance of Bacteroidetes.

Proportion of Firmicutes and Bacteroidetes are plotted for each healthy subject (A) and for each IBS patient (B). Patients are characterized by a relatively higher proportion of Bacteroidetes than healthy controls (P = 0.02, q = 0.09).

Figure 3. Higher relative abundance of two bacterial families and higher alpha-diversity in healthy controls compared to IBS patients.

(A) Erysipelotrichaceae and Ruminococcaceae were found in significantly higher abundance in healthy subjects (n = 66) compared to IBS patients, regardless of their IBS subtype (Kruskal Wallis test, P = 4.7 e-5, q = 0.002 and P = 0.002, q = 0.06, respectively). The two bacterial families belong to the Firmicutes phylum. (B) The Chao1 index based on species-level OTUs was estimated for healthy controls, IBS, IBS-M, IBS-C and IBS-D. Significance (*P = 0.04, **P < 0.003) was determined by Monte Carlo permutations, a non-parametric test.

Figure 4. Dysbiosis at the family and genus level in IBS subtypes.

(A) Four microbial families and one genus discriminate the 66 healthy controls from the 54 patients with IBS-D (Kruskal Wallis test, P < 0.006; q < 0.06). (B) One bacterial family was found in a lower proportion in the 27 IBS-M patients compared to the 66 controls (P = 0.0001, q = 0.006). (C) Comparing the healthy control group with the three IBS subtypes, four genera were enriched in healthy subjects and IBS-C patients compared to IBS-M and IBS-D patients (Kruskal Wallis test, P < 0.003, q ≤ 0.05).

Figure 5

Unweighted UniFrac data redundancy analysis (dbRDA) on the first time point samples constrained by (A) the controls and IBS patients, and constrained by (B) the four groups of participants: controls (n = 66), IBS-C (n = 14), IBS-D (n = 24) and IBS-M (n = 6), discarding patients under treatment.

Figure 6. Methanobacteria from the Euryarchaeota phylum is enriched in controls (n = 66) compared to IBS patients (n = 44) who did not follow any medical treatment (Kruskal Wallis test, P = 0.005, q = 0.05).

Figure 7. Summary of the findings of this study.

= Higher abundance of; = Lower abundance of; = positive correlation with; = negative correlation with.