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. 2024 Jun 6;16(11):1790.
doi: 10.3390/nu16111790.

A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats

Robert S Thompson  1   2 , Samuel J Bowers  3 , Fernando Vargas  4 , Shelby Hopkins  1   2 , Tel Kelley  1 , Antonio Gonzalez  5 , Christopher A Lowry  1   2 , Pieter C Dorrestein  4 , Martha Hotz Vitaterna  3 , Fred W Turek  3 , Rob Knight  5   6   7 , Kenneth P Wright Jr  1   2 , Monika Fleshner  1   2
Affiliations

A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats

Robert S Thompson et al. Nutrients. .

Abstract

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbially modified metabolites over time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides (GOS) and polydextrose (PDX)), compared to a control diet, would consistently impact the gut microbiome and microbially modified bile acids over time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiomes and metabolomes were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered the beta diversity, relative abundance of bacterial genera, and microbially modified bile acids over time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by the prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbially modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites, supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

Keywords: Parabacteroides; Ruminiclostridium 5; bile acid; deoxycholic acid; galactooligosaccharide; metabolome; microbiome; polydextrose; prebiotic.

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Conflict of interest statement

Pieter C. Dorrestein is an advisor and holds equity in Sirenas and Cybele, consulted for MSD animal health in 2023. He is a co-founder, scientific advisor, and holds equity in Ometa Labs, Arome, and Enveda with prior approval by UC San Diego. Rob Knight is a scientific advisory board member, and consultant for BiomeSense, Inc., has equity and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant and scientific advisory board member for DayTwo, and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, and has equity, and is a scientific advisory board member. Christopher A. Lowry is a co-founder, board member, and Chief Scientific Officer of Mycobacteria Therapeutics Corporation. The remaining authors have no known competing financial interests.

Figures

Figure 1
Figure 1
Experimental timeline detailing methods and fecal sampling events. In both studies, animals arrived on postnatal day 23 and were immediately placed on either the control diet or prebiotic diet. In the Northwestern study, fecal samples were taken on experimental (postnatal) days 0 (23), 28 (51), 42 (65), and 51 (74), while in the CU study, fecal samples were taken on experimental days 2 (25), 33 (58), 75 (100), and 94 (119).
Figure 2
Figure 2
Unweighted and weighted UniFrac distance examining β-diversity of the fecal microbiome between studies. (A) In the NW study, unweighted UniFrac distance at experimental day 0 was not different between the control and prebiotic diets, but was different on subsequent days 28, 42, and 51. (B) In the CU study, unweighted UniFrac distance at experimental day 2 was not different between the control and prebiotic diets, but was different on subsequent days 33, 75, and 94. (C) In the NW study, weighted UniFrac distance was not different on day 0 between the control and prebiotic diets, but was different on the remaining days examined. (D) In the CU study, weighted UniFrac distance was significantly different on day 2 between the control and prebiotic diets, an effect that persisted for days 33, 75, and 94.
Figure 3
Figure 3
Consumption of the prebiotic diet produced increases in 9 higher abundance genera between studies. There were consistent increases over time due to the prebiotic diet in: (A) Bacteroides, (B) Parabacteroides, (E) Incertae_Sedis (Ruminiclostridium V), (G) Ruminococcus_gauvreauii_group, and (H) UCG-007. While there were prebiotic diet-induced increases in (C) Clostridia_UCG-014, (D) Christensenellaceae_R-7_group, (F) Parasutterella, and (I) Lachnospiraceae_UCG-006, these genera had less consistent increases over time between studies. * p < 0.05 when compared to control diet.
Figure 4
Figure 4
Consumption of prebiotic diet led to decreases in 6 higher abundance genera between studies. There were consistent decreases over time due to prebiotic diet consumption in: (A) Lachnospiraceae_NK4A136_group, (C) UCG-005, (E) Eubacterium_fissicatena_group, (F) Eubacterium_ruminantium_group, (G) GCA-900066575, and (I) Rikenellaceae_R9-gut_group. There were less consistent effects due to diet between studies in: (B) Eubacterium_ coprostanoligenes_group, (D) Colidextribacter, and (H) Roseburia. * p < 0.05 when compared to prebiotic diet.
Figure 5
Figure 5
There was a significant main effect of the prebiotic diet, increasing (A) the evenness of the alpha diversity in the CU study. In contrast, the main significant effects of the prebiotic diet involved decreases in both (B) Faith’s phylogenetic diversity and (C) the observed features of the alpha diversity in the NW study. There were no significant time-by-diet interactions in regard to the measures of alpha diversity, except at NW in observed features. * p < 0.05 effect of diet.
Figure 6
Figure 6
Consumption of dietary prebiotics affected fecal bile acids between studies, including: (A) muricholic acid beta, (B) deoxycholic acid, and (C) lithocholic acid. Moreover, (D) ursodeoxycholic acid was decreased in the CU study, and (E) glycodeoxycholic acid was decreased in the NW study.
Figure 7
Figure 7
Functional metabolic pathways affected by prebiotic diet, annotated with the MetaCyc metabolic pathway database. Consumption of dietary prebiotics altered the: (A) superpathway UDP-N-acetylglucosamin-derived O-antigen building blocks biosynthesis (PWY-7332) or the UDP-sugar superpathway, the (B) UDP-2,3-diaetamido-2,3-dideoxy-α-D-mannuronate biosynthesis (PWY-7090) or UDP mannuronate pathway, the (C) chondroitin sulfate degradation I (bacterial) pathway (PWY-6572), and the (D) pyrimidine deoxyribonucleotides de novo biosynthesis III pathway (PWY-6545), when compared to the control diet. These effects were consistent between the study sites and over time. * p < 0.05 when compared to control diet.
Figure 8
Figure 8
Network correlations from both study sites, demonstrating consistent networks between inferred functional metabolic pathways and bile acids in prebiotic diet groups. There were no consistent correlation networks present in the control diet groups between the study sites (A,B). The consistent correlation networks in the prebiotic diet groups (C) at NW and (D) at CU imply that the microbially modified secondary bile acid, deoxycholic acid, could be an important component underlying the beneficial effects of dietary prebiotics.
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