Dietary supplement of mushrooms promotes SCFA production and moderately associates with IgA production: A pilot clinical study

Abstract

Background: Mushrooms are rich in dietary fiber, and fiber intake has been reported to increase the levels of short-chain fatty acids (SCFAs). It has also been reported that SCFAs promote immunoglobulin A (IgA) production, indicating involvement in systemic immunity.

Objectives: The objective of this study was to evaluate the effects of mushroom consumption on the amount of intestinal IgA. We also aimed to comprehensively evaluate the gut microbiota and intestinal metabolome and to conduct an exploratory analysis of their relationship with IgA.

Methods: Healthy adults (n = 80) were enrolled in a parallel group trial. Participants consumed a diet with mushrooms or a placebo diet once daily for 4 weeks. Gut microbiota profiles were assessed by sequencing the bacterial 16S ribosomal RNA-encoding gene. Intestinal metabolome profiles were analyzed using capillary electrophoresis-time of flight mass spectrometry (CE-TOFMS).

Results: Mushroom consumption tended to increase IgA levels at 4 weeks of consumption compared to those in the control group (p = 0.0807; Hedges' g = 0.480). The mushroom group had significantly higher levels of intestinal SCFAs, such as butyrate and propionate, than the control group (p = 0.001 and 0.020; Hedges' g = 0.824 and 0.474, respectively). Correlation analysis between the changes in the amount of intestinal IgA and the baseline features of the intestinal environment showed that the increasing amount of intestinal IgA was positively correlated with the baseline levels of SCFAs (Spearman's R = 0.559 and 0.419 for butyrate and propionate, respectively).

Conclusion: Consumption of mushrooms significantly increased the intestinal SCFAs and IgA in some subjects. The increase in intestinal IgA levels was more prominent in subjects with higher SCFA levels at baseline. This finding provides evidence that mushroom alters the intestinal environment, but the intensity of the effect still depends on the baseline intestinal environment. This trial was registered at www.umin.ac.jp as UMIN000043979.

Keywords: gut metabolome; gut microbiome; immunoglobulin A (IgA); mushrooms; short-chain fatty acids (SCFAs).

FIGURE 1

Clinical trial overview and test results for the primary endpoint (intestinal IgA content). (A) Flow diagram of the trial. (B) Clinical trial diagram and description of time points. Subjects were assigned to either the test food (mushroom) group or the placebo food group, and they consumed the assigned food for 4 weeks. (C) Distribution of the primary outcome (intestinal IgA content). The difference between each time point and baseline was calculated and expressed by group and time point. The Wilcoxon rank sum test was performed for comparisons between groups at each intake period (2 or 4 weeks).

FIGURE 2

Effect of mushroom consumption on gut microbiota and metabolome profiles. (A,B) The (A) weighted UniFrac distance for the gut microbiota and (B) Bray–Curtis distance for quantitative metabolome profiles among all samples were calculated and visualized by PcoA. (C,D) After calculating the (C) weighted UniFrac distance of the gut microbiota and (D) Bray–Curtis distance of the quantitative metabolome profiles among all samples, the differences in distances before and after ingestion of the same subjects were evaluated and are shown here for each group. No significant differences were detected in either case (Wilcoxon rank sum test).

FIGURE 3

Effect of mushroom intake on gut microbes and metabolites. The x-axis represents the effect size (Hedges’ g) of mushroom intake compared with the control group. The y-axis represents the logarithm of the Wilcoxon signed-rank test p-value compared with the control group. If absolute value of x-axis is larger than 0.4 and p < 0.05 in y-axis, (A) bacterium or (B) metabolite names were labeled.

FIGURE 4

Correlation analysis with intestinal immunoglobulin A (IgA). Heatmap representing the correlation of the difference in intestinal IgA content between 4-week and 0-week with either (A) baseline values; or (B) differential values of each gut microbe and metabolite abundance and blood measured item. Colors show the Spearman coefficients, and stars show Spearman coefficients’ no-correlation test (*p < 0.05; ^**p < 0.01; ^***p < 0.001). In addition, Wilcoxon rank-sum test was performed on the top 10 subjects and bottom 10 subjects based on increase in IgA level (^†p < 0.05; ^††p < 0.01). (C,D) Scatter plots showing the relationship of (C) butyric acid and (D) Try-Arg-divalent to behavior of intestinal IgA level.