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Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.

ABSTRACT: Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In the preliminary study using rats, the hyperinsulinemia induced by high-fat diet was suppressed by intake of water with 2% (w/v) 1-kestose. In the clinical study using obese-prone volunteers, the fasting serum insulin level was significantly reduced from 6.5 µU/mL (95% CI, 5.5-7.6) to 5.3 (4.6-6.0) by the 12-week intervention with supplementation of 10 g 1-kestose/day, whereas it was not changed by the intervention with placebo (6.2 µU/mL (5.4-7.1) and 6.5 (5.5-7.6) before and after intervention, respectively). The relative abundance of fecal Bifidobacterium was significantly increased to 0.3244 (SD, 0.1526) in 1-kestose-supplemented participants compared to that in control participants (0.1971 (0.1158)). These results suggest that prebiotic intervention using 1-kestose may potentially ameliorate insulin resistance in overweight humans via the modulation of the gut microbiota. UMIN 000028824.

SUBMITTER: Watanabe A

PROVIDER: S-EPMC8470827 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.

Watanabe Ayako A Tochio Takumi T Kadota Yoshihiro Y Takahashi Motoki M Kitaura Yasuyuki Y Ishikawa Hirohito H Yasutake Takanori T Nakano Masahiro M Shinohara Hiroe H Kudo Toru T Nishimoto Yuichiro Y Mizuguchi Yoshinori Y Endo Akihito A Shimomura Yoshiharu Y

Nutrients 20210827 9

Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In ...[more]

PMID: 34578862

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Project description:BackgroundObesity is a complex pathology associated with dysbiosis, metabolic alterations, and low-grade chronic inflammation promoted by immune cells, infiltrating and populating the adipose tissue. Probiotic supplementation was suggested to be capable of counteracting obesity-associated immune and microbial alterations, based on its proven immunomodulatory activity and positive effect on gut microbial balance. Traditional fermented foods represent a natural source of live microbes, including environmental strains with probiotic features, which could transiently colonise the gut. The aim of our work was to evaluate the impact of supplementation with a complex foodborne bacterial consortium on obesity-associated inflammation and gut microbiota composition in a mouse model.MethodsC57BL/6J mice fed a 45% high fat diet (HFD) for 90 days were supplemented with a mixture of foodborne lactic acid bacteria derived from the traditional fermented dairy product "Mozzarella di Bufala Campana" (MBC) or with the commercial probiotic GG strain of Lactobacillus rhamnosus (LGG). Inflammation was assessed in epididymal white adipose tissue (WAT) following HFD. Faecal microbiota composition was studied by next-generation sequencing.ResultsSignificant reduction of epididymal WAT weight was observed in MBC-treated, as compared to LGG and control, animals. Serum metabolic profiling showed correspondingly reduced levels of triglycerides and higher levels of HDL cholesterol, as well as a trend toward reduction of LDL-cholesterol levels. Analysis of the principal leucocyte subpopulations in epididymal WAT revealed increased regulatory T cells and CD4+ cells in MBC microbiota-supplemented mice, as well as decreased macrophage and CD8+ cell numbers, suggesting anti-inflammatory effects. These results were associated with lower levels of pro-inflammatory cytokines and chemokines in WAT explants. Faecal bacterial profiling demonstrated increased Firmicutes/Bacteroidetes ratio in all mice groups following HFD.ConclusionsTaken together, these results indicate a protective effect of MBC microbiota supplementation toward HFD-induced fat accumulation and triglyceride and cholesterol levels, as well as inflammation, suggesting a stronger effect of a mixed microbial consortium vs single-strain probiotic supplementation. The immunomodulatory activity exerted by the MBC microbiota could be due to synergistic interactions within the microbial consortium, highlighting the important role of dietary microbes with yet uncharacterised probiotic effect.

Project description:IntroductionGut microbiota manipulation may be a potential therapeutic target to reduce host energy storage. There is limited information about the effects of probiotics/synbiotics on intestinal microbiota composition in children and adolescents with obesity. The objective of this randomized double-blind placebo-controlled trial was to test the effects of a multispecies synbiotic on intestinal microbiota composition in children and adolescents with exogenous obesity.MethodChildren with exogenous obesity were managed with a standard diet and increased physical activity and were randomly allocated into two groups at a ratio of 1:1; the 1st group received synbiotic supplementation (probiotic mixture including Lactobacillus acidophilus, Lacticaseibacillus. rhamnosus, Bifidobacterium bifidum, Bifidobacterium longum, Enterococcus faecium (total 2.5 × 109 CFU/sachet) and fructo-oligosaccharides (FOS; 625 mg/sachet) for 12 weeks; the 2nd group received placebo once daily for 12 weeks. Fecal samples were obtained before and at the end of the 12-week intervention to characterize the changes in the gut microbiota composition. Detailed metagenomic and bioinformatics analyses were performed.ResultsBefore the intervention, there were no significant differences in alpha diversity indicators between the synbiotic and placebo groups. After 12 weeks of intervention, the observed taxonomic units and Chao 1 were lower in the synbiotic group than at baseline (p < 0.001 for both). No difference for alpha diversity indicators was observed in the placebo group between baseline and 12 weeks of intervention. At the phylum level, the intestinal microbiota composition of the study groups was similar at baseline. The major phyla in the synbiotic group were Firmicutes (66.7%) and Bacteroidetes (18.8%). In the synbiotic group, the Bacteroidetes phylum was higher after 12 weeks than at baseline (24.0% vs. 18.8%, p < 0.01). In the synbiotic group, the Firmicutes/Bacteroidetes ratio was 3.54 at baseline and 2.75 at 12 weeks of intervention (p < 0.05). In the placebo group, the Firmicutes/Bacteroidetes ratio was 4.70 at baseline and 3.54 at 12 weeks of intervention (p < 0.05). After 12 weeks of intervention, the Firmicutes/Bacteroidetes ratio was also lower in the synbiotic group than in the placebo group (p < 0.05). In the synbiotic group, compared with the baseline, we observed a statistically significant increase in the genera Prevotella (5.28-14.4%, p < 0.001) and Dialister (9.68-13.4%; p < 0.05). Compared to baseline, we observed a statistically significant increase in the genera Prevotella (6.4-12.4%, p < 0.01) and Oscillospira (4.95% vs. 5.70%, p < 0.001) in the placebo group. In the synbiotic group, at the end of the intervention, an increase in Prevotella, Coprococcus, Lachnospiraceae (at the genus level) and Prevotella copri, Coprococcus eutactus, Ruminococcus spp. at the species level compared to baseline (predominance of Eubacterium dolichum, Lactobacillus ruminis, Clostridium ramosum, Bulleidia moorei) was observed. At the end of the 12th week of the study, when the synbiotic and placebo groups were compared, Bacteroides eggerthi species were dominant in the placebo group, while Collinsella stercoris species were dominant in the synbiotic group.ConclusionThis study is the first pediatric obesity study to show that a synbiotic treatment is associated with both changes intestinal microbiota composition and decreases in BMI. Trial identifier: NCT05162209 (www.Clinicaltrialsgov).

Project description:Like humans, outbred Sprague-Dawley CD rats exhibit a polygenic pattern of inheritance of the obese phenotype and not all individuals exposed to a high calorie intake develop obesity. We hypothesized that differences in gut microbiota composition account for phenotype differences between obese prone (OP) and obese resistant (OR) rats. We studied the gut microbiota composition of OPand OR rats after a high fat (HF) diet and how they respond to fermentation of resistant starch (RS). In phase 1 of the study 28 OP and 28 OR rats were fed a HF diet. In order to determine causal role of microbiota on phenotypes, In phase 2, a microbiota transplant between the two phenotypes was performed before switching all rats to a HF diet supplemented with 20% RS. We determined microbiota composition by 16S sequencing and predicted microbiota function by PICRUSt2. Despite a similar calorie intake, in phase 2 OP rats gained more weight and accumulated more abdominal fat in both phase 1 and 2 compared to OR rats (P < 0.001; n = 6). The OP rats fermented RS more robustly compared with OR rats with an increase in total bacteria, short chain fatty acids, and increased weight of the cecum, but microbiota of OP rats had much lower alpha diversity and evenness. The microbiota of OP rats, had higher amounts of bacteria from order Bacteroidales, specifically family Muribaculaceae (S24-7), which is known to possess several starch degrading enzymes and was reported in previous studies to increase with fermentation of RS. The OR rats fermented RS less but had higher bacterial diversity and evenness and had significantly higher bacterial counts from phylum Firmicutes particularly order Clostridiales, genus Clostridium and an uncultured bacterium of the genus Akkermansia. The microbiota of OR rats had enhanced bacterial chemotaxis, phosphotransferase system (PTS), and fatty acid biosynthesis compared to OP rats whose microbiota had higher glycan degradation and LPS biosynthesis pathways. The microbiota transplant did not change obesity phenotype or microbiota composition. In conclusion, a higher alpha-diversity and evenness of the microbiota and higher proportions of Clostridiales and Akkermansia in OR rats were associated with a better metabolic phenotype with lower body fat. However, robust RS fermentation caused a lower diversity and evenness and did not result in a leaner phenotype.

Project description:IntroductionThe study was aimed at evaluating the effects of areca nut extract (ANE) on the growth performance, cecal microbiota, and immunity of Wenchang chickens.MethodsFor this study, 42-day-old healthy Wenchang chickens (n = 450) with similar body weight were chosen. The animals were randomly divided into five groups, with six replicates per group and 15 chickens per replicate. One group was fed a basal diet (control; CCK). The remaining four groups were fed a basal diet supplemented with varying ANE concentrations: 0.038, 0.063, 0.100, and 0.151 g/kg, with the groups denoted as CNT1, CNT2, CNT3, and CNT4, respectively. The feeding experiment lasted 35 days. The ligated cecum segments of the control and experimental groups were collected for metabolomic and metagenomic analysis, while the bone marrow samples were extracted for tandem mass tag (TMT)-based proteomic analysis.ResultsAll the experimental groups exhibited significantly higher average daily gain (ADG) and significantly lower feed-to-weight (F/G) ratios than CCK. Metabolomic screening of the cecum contents revealed the presence of 544 differential metabolites, including several gut health-related metabolites, such as xanthine, hydroxy hypoxanthine, 2,5-dimethylhydrazine, ganoderic acid, and 2-aminohexanoic acid. Metagenomic analysis of the cecum contents showed an upregulation in the abundance of Prevotella spp. in the experimental groups. However, we observed no significant differences in the abundances of other cecal microbes at phylum and genus levels. Furthermore, we observed significant associations between Prevotella spp. and the differentially abundant metabolites, such as cherubins, thiaburimamide, and 3,4-dihydroxy-L-phenylalanine, (r)-mevalonate, 5-O-methylalloptaeroxylin, nalidixic acid, and deoxyloganin (p < 0.05). Proteomic analysis revealed that the differentially expressed proteins (such as interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), MHC-BF1, and death domain-associated protein (Daxx)) in the bone marrow of the chickens were primarily enriched in the immune network for IgA production and B cell receptor signaling pathway.ConclusionIn conclusion, dietary ANE supplementation was found to enhance metabolic activity and energy utilization, improve growth performance, modulate cecal microbiota, and strengthen the immunity of Wenchang chickens.

Dataset Information

Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.

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Supplementation of 1-Kestose Modulates the Gut Microbiota Composition to Ameliorate Glucose Metabolism in Obesity-Prone Hosts.

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