Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition?

Lisa Vork, John Penders, Jonna Jalanka, Svetlana Bojic, Sander M J van Kuijk, Anne Salonen, Willem M de Vos, Mirjana Rajilic-Stojanovic, Zsa Zsa R M Weerts, Ad A M Masclee, Marta Pozuelo, Chaysavanh Manichanh, Daisy M A E Jonkers, Lisa Vork, John Penders, Jonna Jalanka, Svetlana Bojic, Sander M J van Kuijk, Anne Salonen, Willem M de Vos, Mirjana Rajilic-Stojanovic, Zsa Zsa R M Weerts, Ad A M Masclee, Marta Pozuelo, Chaysavanh Manichanh, Daisy M A E Jonkers

Abstract

Introduction: Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days.

Methods: Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined.

Results: Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this.

Conclusion: This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual's microbiota at a given time point. NCT00775060.

Keywords: adult; fecal microbiota; intestinal microbiome; irritable bowel syndrome; stool consistency.

Conflict of interest statement

Part of the work of JP is financed by the Joint Programming Initiative A healthy diet for a healthy life (HDHL) Joint Action Intestinal Microbiomics (project number 50–52905–98–599). WV was partially supported by the SIAM Gravitation Grant 024.002.002 and Spinoza Award of the Netherlands Organization for Scientific Research. MR-S performed consultation services for Hemofarm AD, Serbia. ZW was supported to attend a scientific meeting by Will Pharma S.A. AM has received a ZonMw, The Netherlands Organization for Health Research and Development, health care efficiency grant to evaluate efficacy of peppermint oil in IBS, has received an unrestricted research grant from Will Pharma S.A., and received research funding from Allergan and Grünenthal on IBS topics. AM has given scientific advice to Bayer and Kyowa Kirin related to IBS and constipation, and received funding from Pentax Europe GmBH. Part of the work of CM is supported by the Instituto de Salud Carlos III, grant PI/17/00614 co-financed by the European Regional Development Fund (ERDF). Part of the work of DJ is financed by Grant Top Knowledge Institute (Well on Wheat), the Carbokinietics program as part of the NWO-CCC Partnership program and H2020 Nr. 848228/DISCOvERIE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Vork, Penders, Jalanka, Bojic, van Kuijk, Salonen, de Vos, Rajilic-Stojanovic, Weerts, Masclee, Pozuelo, Manichanh and Jonkers.

Figures

Figure 1
Figure 1
(A) Bray Curtis PCoA plot per individual (different colors) and for healthy subjects vs. IBS patients (figure annotations). (B) Average within-subject beta diversity (Bray Curtis Dissimilarity) for healthy subjects vs. IBS patients, significance tested using Mann Whitney U test, NS, not significant (p=0.71).
Figure 2
Figure 2
Redundancy analysis plot based on clr transformed abundancies, and constrained on stool consistency (dry weight percentage), with individual variation partialled-out. Significant association between stool consistency and microbial composition (p = 0.001), mainly driven by bacterial families depicted in the figure.
Figure 3
Figure 3
Redundancy analysis plot based on clr transformed abundancies, and constrained on individual, abdominal pain, and abdominal bloating. Each dot represents an individual sample; IBS patients are depicted by different colors. No significant association between both GI symptoms (p = 0.368 for abdominal pain; p = 0.521 for bloating) and microbial composition.

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