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1.
Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals.
Asnicar, F, Berry, SE, Valdes, AM, Nguyen, LH, Piccinno, G, Drew, DA, Leeming, E, Gibson, R, Le Roy, C, Khatib, HA, et al
Nature medicine. 2021;(2):321-332
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Abstract
The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal postprandial cardiometabolic blood marker measurements were available. We found many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods. Microbial biomarkers of obesity were reproducible across external publicly available cohorts and in agreement with circulating blood metabolites that are indicators of cardiovascular disease risk. While some microbes, such as Prevotella copri and Blastocystis spp., were indicators of favorable postprandial glucose metabolism, overall microbiome composition was predictive for a large panel of cardiometabolic blood markers including fasting and postprandial glycemic, lipemic and inflammatory indices. The panel of intestinal species associated with healthy dietary habits overlapped with those associated with favorable cardiometabolic and postprandial markers, indicating that our large-scale resource can potentially stratify the gut microbiome into generalizable health levels in individuals without clinically manifest disease.
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Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms.
Wilson, B, Eyice, Ö, Koumoutsos, I, Lomer, MC, Irving, PM, Lindsay, JO, Whelan, K
Nutrients. 2021;(10)
Abstract
Prebiotics may promote immune homeostasis and reduce sub-clinical inflammation in humans. This study investigated the effect of prebiotic galactooligosaccharide (GOS) supplementation in colonic inflammation. Seventeen patients with active ulcerative colitis (UC) consumed 2.8 g/d GOS for 6 weeks. At baseline and 6 weeks, gene expression (microarray), fecal calprotectin (ELISA), microbiota (16S rRNA), short-chain fatty acids (SCFAs; gas-liquid chromatography), and clinical outcomes (simple clinical colitis activity index (SCCAI), gastrointestinal symptom rating scale (GSRS), and Bristol stool form scale (BSFS)) were measured. Following prebiotics, clinical scores (SCCAI), fecal calprotectin, SCFAs, and pH were unchanged. Five genes were upregulated and two downregulated. Normal stool proportion (BSFS) increased (49% vs. 70%, p = 0.024), and the incidence (46% vs. 23%, p = 0.016) and severity (0.7 vs. 0.5, p = 0.048) of loose stool (GSRS), along with urgency (SCCAI) scores (1.0 vs. 0.5, p = 0.011), were reduced. In patients with a baseline SCCAI ≤2, prebiotics increased the relative abundance of Bifidobacterium from 1.65% (1.97) to 3.99% (5.37) (p = 0.046) and Christensenellaceae from 0.13% (0.33) to 0.31% (0.76) (p = 0.043). Prebiotics did not lower clinical scores or inflammation but normalized stools. Bifidobacterium and Christensenellaceae proportions only increased in patients with less active diseases, indicating that the prebiotic effect may depend on disease activity. A controlled study is required to validate these observations.
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Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.
Pham, VT, Calatayud, M, Rotsaert, C, Seifert, N, Richard, N, Van den Abbeele, P, Marzorati, M, Steinert, RE
Nutrients. 2021;(4)
Abstract
Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.
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Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study.
Yang, J, Kurnia, P, Henning, SM, Lee, R, Huang, J, Garcia, MC, Surampudi, V, Heber, D, Li, Z
Nutrients. 2021;(11)
Abstract
Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism.
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The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome.
Iribarren, C, Magnusson, MK, Vigsnæs, LK, Aziz, I, Amundsen, ID, Šuligoj, T, Juge, N, Patel, P, Sapnara, M, Johnsen, L, et al
Nutrients. 2021;(11)
Abstract
BACKGROUND Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2'-O-fucosyllactose and lacto-N-neotetraose (2'FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. METHODS Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2'FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. RESULTS Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2'FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2'FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. CONCLUSION Supplementation with 2'FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2'FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.
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Gut microbiota composition influences outcomes of skeletal muscle nutritional intervention via blended protein supplementation in posttransplant patients with hematological malignancies.
Ren, G, Zhang, J, Li, M, Tang, Z, Yang, Z, Cheng, G, Wang, J
Clinical nutrition (Edinburgh, Scotland). 2021;(1):94-102
Abstract
BACKGROUND Skeletal muscle atrophy is an important and independent predictor of survival after hematopoietic stem cell transplantation (HSCT). Our previous study found that soy-whey blended protein (SWP) can improve muscle mass in acute leukemia patients. OBJECTIVE We aimed to explore potential factors that influence muscle outcomes after nutritional intervention. METHODS In this case-control study, 13 patients who received HSCT and failed to improve muscle function within half a year were included. After two months of SWP intervention, the subjects were divided into two groups (MSI: muscle status improved; MNI: muscle status not improved). 16S rDNA sequencing, principal coordinate analysis (PCoA) and the PICRUSt algorithm were used to analyze the composition, structure and function of the intestinal microbiota between the groups. This study was registered in the Chinese Clinical Trial Registry (ChiCTR 1800017765). RESULTS SWP significantly improved muscle status (muscle area: from 330.4 mm2 to 384.8 mm2, p = 0.02; muscle strength: from 19.2 kg to 21.3 kg, p = 0.04). However, there were a small number of subjects whose muscle status was not effectively improved. After SWP intervention, the diversity (Shannon: from 1.7 to 3.8, p = 0.01; Simpson: from 0.6 to 0.8, p = 0.015) of the intestinal microbiota in the MSI group increased significantly, whereas that in the MNI group did not. Principal component analysis (PCA) revealed separate groupings of the microbiota of the Baseline-MSI and Endpoint-MSI time points in the MSI group. Opposite patterns of microbial abundance change were found between the MSI group (75% of changed genera were increased) and the MNI group (80% of changed genera were decreased). Three bacterial taxa (negative correlation: Streptococcus; positive correlations: Ruminococcus and Veillonella) were significantly related to muscle improvement outcomes. Both pentose phosphate (p = 0.048) and amino acid biosynthesis (p = 0.039), which are related to muscle metabolism, were found to be significantly changed in the MSI group through PICRUSt algorithm prediction. CONCLUSIONS Our results suggest that the intestinal microbiota plays important roles in the regulation of muscle metabolism.
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Effects of Malted Rice Amazake on Constipation Symptoms and Gut Microbiota in Children and Adults with Severe Motor and Intellectual Disabilities: A Pilot Study.
Kageyama, S, Inoue, R, Hosomi, K, Park, J, Yumioka, H, Suka, T, Kurohashi, Y, Teramoto, K, Syauki, AY, Doi, M, et al
Nutrients. 2021;(12)
Abstract
Constipation is a frequent complication in patients with severe motor and intellectual disabilities (SMID). The aim of this study was to investigate changes in constipation symptoms and gut microbiota associated with the intake of malted rice amazake, a fermented food in Japan, in patients with SMID. Ten patients consumed the test food for six weeks, and their physical condition, dietary and medication status, and constipation assessment scale (CAS) were investigated. Comprehensive fecal microbiome analysis using the 16S rRNA sequence method was performed. The results showed a significant decrease in CAS, and a significant increase in Lactobacillales and decrease in Escherichia-Shigella after consuming malted rice amazake. To investigate the difference in the effects of malted rice amazake consumption, based on the characteristics of the original gut microbiota, the patients were grouped according to the similarity of their gut microbiota before the intervention; Firmicutes-rich Group 1 (n = 5), Actinobacteria-rich Group 2 (n = 4), and Proteobacteria-rich Group 3 (n = 1). The CAS decreased in Groups 1 and 2. The relative abundance of Bifidobacterium showed an increasing tendency both overall and in Group 1, but it was originally higher in Group 2. Our results suggest that malted rice amazake consumption reduces constipation symptoms and simultaneously changes the gut microbiota, but the changes may vary depending on the original composition of the gut microbiota.
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Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.
Bajaj, JS, Shamsaddini, A, Fagan, A, Sterling, RK, Gavis, E, Khoruts, A, Fuchs, M, Lee, H, Sikaroodi, M, Gillevet, PM
Hepatology communications. 2021;(2):258-271
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Abstract
Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.
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Beneficial effects of lactitol on the composition of gut microbiota in constipated patients.
Li, XQ, Zhang, XM, Wu, X, Lan, Y, Xu, L, Meng, XC, Li, JN
Journal of digestive diseases. 2020;(8):445-453
Abstract
OBJECTIVE To explore the changes in microbial composition and the corresponding impact after lactitol treatment in constipated patients. METHODS Altogether 29 consecutive outpatients diagnosed with chronic constipation from three centers were recruited and stratified based on their history of diabetes mellitus. All patients were administered with oral lactitol for 2 weeks, and a symptoms diary of constipation was recorded. Fecal samples were collected before and after lactitol treatment, and were analyzed by 16S rRNA sequencing and real-time polymerase chain reaction (PCR) to detect gut microbiota. RESULTS Twenty patients with diabetes mellitus and nine without, all with chronic constipation, were enrolled in this study. After 2-week administration of lactitol, their subscale scores and constipation symptoms significantly decreased (P < 0.05). An analysis of fecal flora using 16S rRNA sequencing found an increasing trend of abundance of Bifidobacterium in the post-lactitol group (P = 0.08). Actinobacteria, Actinobacteria, Bifidobacteriales, Bifidobacteriaceae and Bifidobacterium were significantly more abundant after lactitol administration. Real-time PCR showed significantly high DNA copy numbers of Bifidobacterium after lactitol treatment (1.39 × 1010 vs 2.74 × 109 copies/μL, P = 0.01). The results of 16S rRNA sequencing and real-time PCR illustrated an increasing trend of Bifidobacterium in both patients with and without diabetes. In addition, Bifidobacterium was negatively correlated with constipation subscale scores. CONCLUSIONS Alterations in fecal flora composition after lactitol supplementation, especially in terms of an increasing trend of Bifidobacterium, alleviated constipation symptoms. Lactitol may be a promising prebiotic candidate for patients with constipation, regardless of diabetes mellitus.
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Whole Blueberry and Isolated Polyphenol-Rich Fractions Modulate Specific Gut Microbes in an In Vitro Colon Model and in a Pilot Study in Human Consumers.
Ntemiri, A, Ghosh, TS, Gheller, ME, Tran, TTT, Blum, JE, Pellanda, P, Vlckova, K, Neto, MC, Howell, A, Thalacker-Mercer, A, et al
Nutrients. 2020;(9)
Abstract
Blueberry (BB) consumption is linked to improved health. The bioconversion of the polyphenolic content of BB by fermentative bacteria in the large intestine may be a necessary step for the health benefits attributed to BB consumption. The identification of specific gut microbiota taxa that respond to BB consumption and that mediate the bioconversion of consumed polyphenolic compounds into bioactive forms is required to improve our understanding of how polyphenols impact human health. We tested the ability of polyphenol-rich fractions purified from whole BB-namely, anthocyanins/flavonol glycosides (ANTH/FLAV), proanthocyanidins (PACs), the sugar/acid fraction (S/A), and total polyphenols (TPP)-to modulate the fecal microbiota composition of healthy adults in an in vitro colon system. In a parallel pilot study, we tested the effect of consuming 38 g of freeze-dried BB powder per day for 6 weeks on the fecal microbiota of 17 women in two age groups (i.e., young and older). The BB ingredients had a distinct effect on the fecal microbiota composition in the artificial colon model. The ANTH/FLAV and PAC fractions were more effective in promoting microbiome alpha diversity compared to S/A and TPP, and these effects were attributed to differentially responsive taxa. Dietary enrichment with BB resulted in a moderate increase in the diversity of the microbiota of the older subjects but not in younger subjects, and certain health-relevant taxa were significantly associated with BB consumption. Alterations in the abundance of some gut bacteria correlated not only with BB consumption but also with increased antioxidant activity in blood. Collectively, these pilot data support the notion that BB consumption is associated with gut microbiota changes and health benefits.