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Letter
Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating
  1. Tom Holvoet1,
  2. Marie Joossens2,3,4,
  3. Jun Wang2,3,
  4. Jerina Boelens5,
  5. Bruno Verhasselt5,
  6. Debby Laukens1,
  7. Hans van Vlierberghe1,
  8. Pieter Hindryckx1,
  9. Martine De Vos1,
  10. Danny De Looze1,
  11. Jeroen Raes2,3
  1. 1Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
  2. 2KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute, B-3000 Leuven, Belgium
  3. 3VIB, Center for the Biology of Disease, Leuven, Belgium
  4. 4Faculty of Sciences and Bioengineering Sciences, Microbiology Unit, Vrije Universiteit Brussel, Brussels, Belgium
  5. 5Department of Medical Microbiology, Ghent University Hospital, Ghent, Belgium
  1. Correspondence to Dr Jeroen Raes, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; jeroen.raes{at}gmail.com TH, MJ, DDL and JR contributed equally.

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We read with interest the work by Halmos et al1 in which they describe the effects of dietary FODMAP (Fermentable Oligo-, Di- and Mono- saccharides And Polyols) restriction in patients with IBS on the intestinal microbiota. They showed that low FODMAP intake was associated with reduced total bacterial and lower relative abundance of butyrate-producing Clostridium cluster XIVa, changes that are generally considered unfavourable.2 Therefore, they discourage long-term dietary FODMAP restriction, a suggestion also supported by the recent work of McIntosh and colleagues who noticed unfavourable changes in both microbiota and metabolome of patients with IBS who were on a low FODMAP diet.3 Although low FODMAP intake reduces GI symptoms in almost 75% of patients with IBS, the effects of this diet on the intestinal microbiota might be disadvantageous in the long run.

Combining these observations with the important role for the intestinal microbiota in IBS pathogenesis,4 we report here faecal microbiota transplantation (FMT) as an alternative to FODMAP restriction in patients with IBS. We applied FMT in 12 refractory IBS patients (Rome III criteria) with intermittent diarrhoea and severe bloating, and mapped the associated microbiota changes after therapy 5 ,6 (see online supplementary file). In our cohort, the median disease duration was 14.5 years (5–40) and patients (8/12 female) had undergone at least three conventional treatment attempts prior to inclusion (see online supplementary table S1). Consecutive faecal samples were collected from the last seven patients for microbiome analyses.

In this study nine patients (75%) met the primary endpoint being: ‘adequate relief of global IBS symptoms and abdominal bloating’, 12 weeks after FMT. A significant reduction in general abdominal discomfort (−21%), abdominal pain (−26%), bloating (−35%) and flatulence (−37%) was reported. The overall quality of life also improved significantly (+12.9%) (see online supplementary tables S2 and S3, figure 1). Responders were followed up and 7/9 (78%) still reported significant relief of IBS symptoms after a period of 1 year, suggesting long-lasting effects of FMT.

Figure 1

Changes in specific IBS-related symptoms at week 12 post-FMT. Lines in green represent responders to the FMT, lines in red represent non-responders. Wilcoxon's signed ranks test. FMT, faecal microbiota transplantation.

Microbiota analysis showed no community differences between patients and donors and no difference in microbial dissimilarity between patient–donor responders and non-responder pairs at baseline. However, we observed a trend of higher Streptococcus counts in donors compared with patients (uncorrected p=0.011) and successful donors tended to have higher baseline counts of Streptococcus compared with non-successful donors (figure 2). Interestingly, we also observed a trend of higher enrichment potential in responders compared with non-responders (figure 2). In line with earlier observations in IBD, the median number of successfully transferred phylotypes was also higher in responders (n=6) versus non-responders (n=2.5) (not significant).7

Figure 2

Baseline microbial differences between donors and patients and microbial differences according to the response to treatment. (A) The observed tendency for higher Streptococcus counts at baseline in donors compared with patients (uncorrected p=0.011). (B) The trend for higher baseline counts of Streptococcus in successful donors compared with non-successful donors. (C) The differences in delta richness (donor minus patient) values between patients with IBS responding to the FMT versus non-responders (Chao1 richness: p=0.095). FMT, faecal microbiota transplantation.

With this open-label FMT study in patients with IBS, we found a similar response rate as for the low-FODMAP diet. Interestingly, positive effects on IBS-related symptoms seem to be linked to changes in the intestinal microbiota due to FMT. This study suggests FMT as a possible treatment option for IBS and supports correlations between abnormalities in the intestinal microbiota and IBS.

The main limitation of our study is its design as an open-label trial. Of note, however, placebo response rates in similar IBS patient cohorts are reported to be approximately 37.5%, which is considerably lower than the response rate of 75% that we report here.8 Nonetheless, double-blind, placebo-controlled trials, addressing also microbial changes, are necessary to provide clear answers about the applicability of FMT in IBS and are currently on-going both in our centre (NCT02299973) and elsewhere (NCT02092402; NCT02154867).

Acknowledgments

The authors would like to thank Saskia Van Damme, Thalita Van Hulle, Jolien De Keukelaere, Joris Van Caenegem, Jen Vandevijver, Kimberley Claus, Tine De Lepeleire, Saskia Verhofstede, Petra Premereur, Leen Rymenans and Chloe Verspecht for technical support.

References

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Footnotes

  • Twitter Follow Marie Joossens at @JoossensM

  • Contributors Study concept and design: TH, MDV, DDL, MJ, and JR. Acquisition, analysis or interpretation of data: TH, DDL, MJ, JW, JB, and JR. Drafting of the manuscript: TH and MJ. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: TH, JW, and MJ. Obtained funding: DL, MDV, MJ, BV, JB, HVB, DDL and JR. Administrative, technical or material support: TH, JB, MJ, HVB, BV, JR, and DL. Study supervision: DDL, MDV, BV, and JR. Final approval of manuscript as submitted: all authors. Guarantors of the article: DDL and JR.

  • Funding TH, MJ, DL, BV and JW are supported by fellowships from the Research Foundation—Flanders (FWO).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethical Committee University Hospital Ghent.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data sharing statement All data are available to TH, MJ, JR and DL.

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