A starch- and sucrose-reduced dietary intervention in irritable bowel syndrome patients produced a shift in gut microbiota composition along with changes in phylum, genus, and amplicon sequence variant abundances, without affecting the micro-RNA levels

Clara Nilholm, Lokeshwaran Manoharan, Bodil Roth, Mauro D'Amato, Bodil Ohlsson, Clara Nilholm, Lokeshwaran Manoharan, Bodil Roth, Mauro D'Amato, Bodil Ohlsson

Abstract

Background/aim: A randomized clinical trial with a starch- and sucrose-reduced diet (SSRD) in irritable bowel syndrome (IBS) patients has shown clear improvement of participants' symptoms. The present study aimed to explore the effects of the SSRD on the gut microbiota and circulating micro-RNA in relation to nutrient intake and gastrointestinal symptoms.

Methods: IBS patients were randomized to a 4-week SSRD intervention (n = 80) or control group (n = 25); habitual diet). At baseline and 4 weeks, blood and fecal samples, 4 day-dietary records, and symptom questionnaires were collected, that is, Rome IV questionnaires, IBS-symptom severity score (IBS-SSS) and visual analog scale for IBS (VAS-IBS). Micro-RNA was analyzed in blood and microbiota in faeces by 16S rRNA from regions V1-V2.

Results: The alpha diversity was unaffected, whereas beta diversity was decreased (p < 0.001) along with increased abundance of Proteobacteria (p = 0.0036) and decreased abundance of Bacteroidetes phyla (p < 0.001) in the intervention group at 4 weeks. Few changes were noted in the controls. The shift in beta diversity and phyla abundance correlated with decreased intakes of carbohydrates, disaccharides, and starch and increased fat and protein intakes. Proteobacteria abundance also correlated positively (R2 = 0.07, p = 0.0016), and Bacteroidetes negatively (R2 = 0.07, p = 0.0017), with reduced total IBS-SSS. Specific genera, for example, Eubacterium eligens, Lachnospiraceae UCG-001, Victivallis, and Lachnospira increased significantly in the intervention group (p < 0.001 for all), whereas Marvinbryantia, DTU089 (Ruminoccocaceae family), Enterorhabdus, and Olsenella decreased, together with changes in amplicon sequence variant (ASV) levels. Modest changes of genus and ASV abundance were observed in the control group. No changes were observed in micro-RNA expression in either group.

Conclusion: The SSRD induced a shift in beta diversity along with several bacteria at different levels, associated with changes in nutrient intakes and reduced gastrointestinal symptoms. No corresponding changes were observed in the control group. Neither the nutrient intake nor the microbiota changes affected micro-RNA expression. The study was registered at ClinicalTrials.gov data base (NCT03306381).

Keywords: gastrointestinal symptoms; gut microbiota; irritable bowel syndrome; micro-RNA; starch- and sucrose-reduced diet.

Conflict of interest statement

There are no competing interests.

© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.

Figures

FIGURE 1
FIGURE 1
Alpha diversity indices (Observed amplicon sequence variants and Shannon‐Weiner) in the intervention versus control group. (a) Before the study (T0) and (b) After the study (T1)
FIGURE 2
FIGURE 2
PCA plot of beta diversity at baseline (T0) and 4 weeks (T1) in (a) the control group and (b) the intervention group. E% = energy percent. PCA biplot showing delta nutrient variables (arrows) significantly correlated to the community composition of each participant in the intervention group (b) (through ‘envfit()’). Ellipses show the distribution of the samples according to time‐point (V1 = baseline; V2 = 4 weeks). The variance of the variables is approximated by arrow length, and their correlations by the angles between them. Observations with similar PCA component score correspond to proximity between individual points. The biplot shows that community composition correlated with self‐reported changes in nutrient intakes of disaccharides (g), carbohydrates (g), starch (g and E%) and protein (E%) (p < 0.05 for all, and p < 0.01 for protein). Further, changes in disaccharides, carbohydrates and starch are shown to be positively correlated to each other, while negatively correlated to change in protein E%
FIGURE 3
FIGURE 3
Relative abundance of phyla in the intervention and control group before and after the sucrose‐reduced diet intervention
FIGURE 4
FIGURE 4
E% = energy percentage. Correlations between the abundance of Proteobacteria and Bacteroidetes and nutrients and total irritable bowel syndrome‐symptom severity score (IBS‐SSS) calculated through ‘envfit()’ within the control group (4a), and regarding Proteobacteria (4b) and Bacteroidetes (4c) in the intervention group. p < 0.05 was considered statistically significant
FIGURE 4
FIGURE 4
E% = energy percentage. Correlations between the abundance of Proteobacteria and Bacteroidetes and nutrients and total irritable bowel syndrome‐symptom severity score (IBS‐SSS) calculated through ‘envfit()’ within the control group (4a), and regarding Proteobacteria (4b) and Bacteroidetes (4c) in the intervention group. p < 0.05 was considered statistically significant
FIGURE 4
FIGURE 4
E% = energy percentage. Correlations between the abundance of Proteobacteria and Bacteroidetes and nutrients and total irritable bowel syndrome‐symptom severity score (IBS‐SSS) calculated through ‘envfit()’ within the control group (4a), and regarding Proteobacteria (4b) and Bacteroidetes (4c) in the intervention group. p < 0.05 was considered statistically significant
FIGURE 5
FIGURE 5
Differential abundance of genera (baseline to 4 weeks) in (a) The control group and (b) The intervention group
FIGURE 6
FIGURE 6
PCA plot of miRNA expression at baseline (T0) and 4 weeks (T1) in (a) the control group and (b) the intervention group. PCA biplot showing the miRNA expression of each participant in the intervention group (b). V1 = baseline; V2 = 4 weeks p > 0.05 for all

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