Precision Microbiome Modulation with Structurally Distinct Type-4 Resistant Starches (OR23-08-19)

Abstract Objectives The gut microbiota is linked to a wide range of pathologies, making it a promising target for improving health. Modulation of the gut microbiota can be achieved by dietary fibers, such as resistant starches, which have demonstrated a role in the prevention of these diseases. However, it is unknown if targeted manipulation of gut microbiota composition, and especially function can be achieved by specific doses of structurally similar yet district fibers. The objective of this study was to compare the effect and dose-response of three different type-4 resistant starches (RS4s) on microbiome composition and function. Methods Using a randomized, double blind, placebo controlled, four arm design, 40 subjects were assigned to consume either one of three RS4s (derived from hi-maize, potato, or tapioca) or a digestible starch for 4 weeks. The fiber dose was raised each week from 0 to 50 g/d, and fecal samples were collected at the end of each week. Microbiota composition and SCFA were assessed by 16S RNA gene sequencing and gas chromatography, respectively. Results Maize and tapioca RS4s, at doses ≥35 g/d, significantly affected the global composition of the microbiota, decreasing α-diversity and increasing β-diversity compared to baseline. Interestingly, effects of RS4s on microbiota composition and fecal SCFA were distinct and reflected differences in RS4 structure. Maize RS4 enriched Operational Taxonomic Units related to Eubacterium rectale [100% ID], Ruminococcus spp [97.9% ID], and Bifidobacterium adolescentis [100% ID], and increased butyrate. Although there was overlap in the enrichment of B. adolescentis, tapioca RS4 enriched Parabacteroides distasonis [100% ID] and Eisenbergiella spp [94% ID] (but not E. rectale or Ruminococcus spp), and increased propionate. These affects were dose-dependent with a plateau at the 35 g/d dose. In contrast, potato RS4 and digestible starch did not significantly modulate the microbiome. Conclusions These findings provide essential information on how chemical differences in starch structure can result in specific and dose-dependent alterations of the gut microbiome, providing a basis for precision microbiome modulation through nutritional strategies. Funding Sources This work was supported by Ingredion Incorporated, and by the Campus Alberta Innovation Program, CIHR, and the Canada Foundation for Innovation.

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Anti-Acid Drug Treatment Induces Changes in the Gut Microbiome Composition of Hemodialysis Patients

Microorganisms ◽

10.3390/microorganisms9020286 ◽

2021 ◽

Vol 9 (2) ◽

pp. 286

Author(s):

Yi-Ting Lin ◽

Ting-Yun Lin ◽

Szu-Chun Hung ◽

Po-Yu Liu ◽

Ping-Hsun Wu ◽

...

Keyword(s):

Random Forest ◽

Gut Microbiota ◽

Gut Microbiome ◽

Hemodialysis Patients ◽

Microbiota Composition ◽

Microbial Composition ◽

Linear Discriminant ◽

H2 Blocker ◽

Α Diversity ◽

16S Rna

Anti-acid drugs, proton pump inhibitor (PPI) and histamine-2 blocker (H2-blocker), are commonly prescribed to treat gastrointestinal disorders. These anti-acid drugs alter gut microbiota in the general population, but their effects are not known in hemodialysis patients. Hence, we investigated the microbiota composition in hemodialysis patients treated with PPIs or H2-blocker. Among 193 hemodialysis patients, we identified 32 H2-blocker users, 23 PPI users, and 138 no anti-acid drug subjects. Fecal samples were obtained to analyze the gut microbiome using 16S RNA amplicon sequencing. Differences in the microbial composition of the H2-blocker users, PPI users, and controls were assessed using linear discriminant analysis effect size and the random forest algorithm. The species richness or evenness (α-diversity) was similar among the three groups, whereas the inter-individual diversity (β-diversity) was different between H2-blocker users, PPI users, and controls. Hemodialysis patients treated with H2-blocker and PPIs had a higher microbial dysbiosis index than the controls, with a significant increase in the genera Provetella 2, Phascolarctobacterium, Christensenellaceae R-7 group, and Eubacterium oxidoreducens group in H2-blocker users, and Streptococcus and Veillonella in PPI users. In addition, compared to the H2-blocker users, there was a significant enrichment of the genera Streptococcus in PPI users, as confirmed by the random forest analysis and the confounder-adjusted regression model. In conclusion, PPIs significantly changed the gut microbiota composition in hemodialysis patients compared to H2-blocker users or controls. Importantly, the Streptococcus genus was significantly increased in PPI treatment. These findings caution against the overuse of PPIs.

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Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz075 ◽

2019 ◽

Vol 110 (2) ◽

pp. 316-329 ◽

Cited By ~ 15

Author(s):

Geoffrey Istas ◽

Eleanor Wood ◽

Melanie Le Sayec ◽

Claudia Rawlings ◽

Jeeyoung Yoon ◽

...

Keyword(s):

Gut Microbiota ◽

Vascular Function ◽

Cardiovascular Health ◽

Controlled Trial ◽

Healthy Population ◽

Microbiota Composition ◽

Double Blind ◽

Phenolic Metabolites ◽

Healthy Men ◽

Gut Microbiota Composition

ABSTRACT Background Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. Objectives The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. Methods A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. Results Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% ± 0.4% (95% CI: 0.13%, 1.72%) and 1.2% ± 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% ± 0.3%, P = 0.003) and 12 wk later (1.5% ± 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. Conclusions In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.

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Microbial signature in IgE-mediated food allergies

Genome Medicine ◽

10.1186/s13073-020-00789-4 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Michael R. Goldberg ◽

Hadar Mor ◽

Dafna Magid Neriya ◽

Faiga Magzal ◽

Efrat Muller ◽

...

Keyword(s):

Food Allergy ◽

Gut Microbiota ◽

Learning Algorithm ◽

Area Under The Curve ◽

Food Allergies ◽

Rrna Gene ◽

Microbiota Composition ◽

Α Diversity ◽

Ige Mediated ◽

Gut Microbiota Composition

Abstract Background Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. Methods To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). Results The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and β-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. Conclusions Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

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Mo1320 IMPACT OF HUMAN MILK OLIGOSACCHARIDES ON THE GUT MICROBIOTA COMPOSITION FROM IRRITABLE BOWEL SYNDROME PATIENTS; A PARALLEL DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Gastroenterology ◽

10.1016/s0016-5085(20)32798-0 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-848

Author(s):

Louise K. Vigsnæs ◽

Cristina Iribarren ◽

Maria K. Magnusson ◽

Ingvild D. Amundsen ◽

Bruce McConnell ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Human Milk ◽

Controlled Trial ◽

Microbiota Composition ◽

Human Milk Oligosaccharides ◽

Milk Oligosaccharides ◽

Double Blind ◽

Irritable Bowel ◽

Gut Microbiota Composition

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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

Nutrients ◽

10.3390/nu13113836 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3836

Author(s):

Cristina Iribarren ◽

Maria K. Magnusson ◽

Louise K. Vigsnæs ◽

Imran Aziz ◽

Ingvild Dybdrodt Amundsen ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Human Milk ◽

Microbiota Composition ◽

Bifidobacterium Adolescentis ◽

Metabolite Profiles ◽

Mucosal Response ◽

Irritable Bowel ◽

Plasma Metabolite ◽

Gut Microbiota Composition

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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Analyzing Type 2 Diabetes Associations with the Gut Microbiome in Individuals from Two Ethnic Backgrounds Living in the Same Geographic Area

Nutrients ◽

10.3390/nu13093289 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3289

Author(s):

Manon Balvers ◽

Mélanie Deschasaux ◽

Bert-Jan van den Born ◽

Koos Zwinderman ◽

Max Nieuwdorp ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiota ◽

South Asian ◽

Gut Microbiome ◽

Geographical Area ◽

Microbiota Composition ◽

Α Diversity ◽

Functional Pathways ◽

Gut Microbiota Composition

It is currently unknown whether associations between gut microbiota composition and type 2 diabetes (T2D) differ according to the ethnic background of individuals. Thus, we studied these associations in participants from two ethnicities characterized by a high T2D prevalence and living in the same geographical area, using the Healthy Life In Urban Settings (HELIUS) study. We included 111 and 128 T2D participants on metformin (Met-T2D), 78 and 49 treatment-naïve T2D (TN-T2D) participants, as well as a 1:1 matched group of healthy controls from, respectively, African Surinamese and South-Asian Surinamese descent. Fecal microbiome profiles were obtained through 16S rRNA gene sequencing. Univariate and machine learning analyses were used to explore the associations between T2D and the composition and function of the gut microbiome in both ethnicities, comparing Met-T2D and TN-T2D participants to their respective healthy control. We found a lower α-diversity for South-Asian Surinamese TN-T2D participants but no significant associations between TN-T2D status and the abundance of bacterial taxa or functional pathways. In African Surinamese participants, we did not find any association between TN-T2D status and the gut microbiome. With respect to Met-T2D participants, we identified several bacterial taxa and functional pathways with a significantly altered abundance in both ethnicities. More alterations were observed in South-Asian Surinamese. Some altered taxa and pathways observed in both ethnicities were previously related to metformin use. This included a strong negative association between the abundance of Romboutsia and Met-T2D status. Other bacterial taxa were consistent with previous observations in T2D, including reduced butyrate producers such as Anaerostipes hadrus. Hence, our results highlighted both shared and unique gut microbial biomarkers of Met-T2D in individuals from different ethnicities but living in the same geographical area. Future research using higher-resolution shotgun sequencing is needed to clarify the role of ethnicity in the association between T2D and gut microbiota composition.

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Fecal Supernatant from Adult with Autism Spectrum Disorder Alters Digestive Functions, Intestinal Epithelial Barrier, and Enteric Nervous System

Microorganisms ◽

10.3390/microorganisms9081723 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1723

Author(s):

Jacques Gonzales ◽

Justine Marchix ◽

Laetitia Aymeric ◽

Catherine Le Berre-Scoul ◽

Johanna Zoppi ◽

...

Keyword(s):

Nervous System ◽

Gut Microbiota ◽

Enteric Nervous System ◽

Fecal Microbiota ◽

Autism Spectrum ◽

Repetitive Behaviors ◽

Rrna Gene ◽

Intestinal Epithelial ◽

Microbiota Composition ◽

Α Diversity

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders defined by impaired social interactions and communication with repetitive behaviors, activities, or interests. Gastrointestinal (GI) disturbances and gut microbiota dysbiosis are frequently associated with ASD in childhood. However, it is not known whether microbiota dysbiosis in ASD patients also occurs in adulthood. Further, the consequences of altered gut microbiota on digestive functions and the enteric nervous system (ENS) remain unexplored. Therefore, we studied, in mice, the ability offecal supernatant (FS) from adult ASD patients to induce GI dysfunctions and ENS remodeling. First, the analyses of the fecal microbiota composition in adult ASD patients indicated a reduced α-diversity and increased abundance of three bacterial 16S rRNA gene amplicon sequence variants compared to healthy controls (HC). The transfer of FS from ASD patients (FS–ASD) to mice decreased colonic barrier permeability by 29% and 58% compared to FS–HC for paracellular and transcellular permeability, respectively. These effects are associated with the reduced expression of the tight junction proteins JAM-A, ZO-2, cingulin, and proinflammatory cytokines TNFα and IL1β. In addition, the expression of glial and neuronal molecules was reduced by FS–ASD as compared to FS-HC in particular for those involved in neuronal connectivity (βIII-tubulin and synapsin decreased by 31% and 67%, respectively). Our data suggest that changes in microbiota composition in ASD may contribute to GI alterations, and in part, via ENS remodeling.

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Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial

Acta Endocrinologica ◽

10.1530/eje-18-0826 ◽

2019 ◽

Vol 180 (3) ◽

pp. 165-176 ◽

Cited By ~ 14

Author(s):

Hanieh-Sadat Ejtahed ◽

Raul Y Tito ◽

Seyed-Davar Siadat ◽

Shirin Hasani-Ranjbar ◽

Zahra Hoseini-Tavassol ◽

...

Keyword(s):

Clinical Trial ◽

Gut Microbiota ◽

Amplicon Sequencing ◽

Fecal Microbiota ◽

Pharmacological Therapy ◽

Microbiota Composition ◽

Obese Women ◽

Double Blind ◽

Baseline Values ◽

Gut Microbiota Composition

Objective The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD). Design Randomized double-blind parallel-group clinical trial Methods Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. Results Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigella abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002). Conclusions Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.

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Dysbiosis of Fecal Microbiota in Allergic Rhinitis Patients

American Journal of Rhinology and Allergy ◽

10.1177/1945892420920477 ◽

2020 ◽

Vol 34 (5) ◽

pp. 650-660 ◽

Cited By ~ 1

Author(s):

Xiang Liu ◽

Jing Tao ◽

Jing Li ◽

Xiaolin Cao ◽

Yong Li ◽

...

Keyword(s):

Allergic Rhinitis ◽

Statistical Analysis ◽

Gut Microbiota ◽

Study Groups ◽

Fecal Microbiota ◽

Rrna Gene ◽

Microbiota Composition ◽

Linear Discriminant ◽

Α Diversity ◽

Gut Microbiota Composition

Background The gut microbiota plays an important role in shaping the immune system and may be closely connected to the development of allergic diseases. Objective This study aimed to determine the gut microbiota composition in Chinese allergic rhinitis (AR) patients as compared with healthy controls (HCs). Methods We collected stool samples from 93 AR patients and 72 age- and sex-matched HCs. Gut microbiota composition was analyzed using QIIME targeting the 16S rRNA gene. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Statistical analysis was performed using the R program, linear discriminant analysis effect size (LefSe), analysis of QIIME, and statistical analysis of metagenomic profiles, among other tests. Results Compared with HCs, AR patients had significantly lower gut-microbiota α-diversity ( P < .001). The gut microbiota composition significantly differed between the 2 study groups. At the phylum level, the relative abundance of Bacteroidetes was higher while those of Actinobacteria and Proteobacteria were lower in the AR group than in the HC group ( P < .001, q < 0.001). At the genus level, Escherichia-Shigella, Prevotella, and Parabacteroides ( P < .001, q < 0.001) had significantly higher relative abundances in the AR group than in the HC group. LefSe analysis indicated that Escherichia-Shigella, Lachnoclostridium, Parabacteroides, and Dialister were potential biomarkers for AR. In addition, predictive metagenome functional analysis showed that pyruvate, porphyrin, chlorophyll, purine metabolism, and peptidoglycan biosynthesis significantly differed between the AR and HC groups. Conclusion A comparison of the gut microbiota of AR patients and HCs suggested that dysbiosis of the fecal microbiota is involved in the development of AR. The present results may reveal key differences and identify targets for preventive or therapeutic intervention.

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