scholarly journals Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2220 ◽  
Author(s):  
Clara E. Cho ◽  
Niklas D. J. Aardema ◽  
Madison L. Bunnell ◽  
Deanna P. Larson ◽  
Sheryl S. Aguilar ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Disease Risk ◽  
Microbiota Composition ◽  
Dietary Recommendations ◽  
Healthy Men ◽  
Choline Bitartrate ◽  
Double Blinded ◽  
Further Development ◽  
Gut Microbiota Composition

Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk

scholarly journals Free Choline, but Not Phosphatidylcholine, Elevates Circulating Trimethylamine-N-oxide and This Response Is Modified by the Gut Microbiota Composition in Healthy Men

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 379-379
Author(s):  
Clara Cho ◽  
Niklas D J Aardema ◽  
Madison L Bunnell ◽  
Deanna P Larson ◽  
Sheryl S Aguilar ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Gut Microbiota ◽  
Alpha Diversity ◽  
Random Order ◽  
Microbiota Composition ◽  
Dietary Recommendations ◽  
Healthy Men ◽  
Choline Bitartrate ◽  
Free Choline ◽  
Gut Microbiota Composition

Abstract Objectives Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. However, the contributions of different forms of choline and gut microbiota composition on TMAO production are largely unknown. The objectives of this study were to: 1) compare acute TMAO response to meals containing free choline (choline bitartrate) versus fat-soluble choline (phosphatidylcholine) and 2) to determine the effects of gut microbiota composition on TMAO response. Methods In a controlled, double-blinded, cross-over study, healthy men (n = 37) were provided meals containing (i) 600 mg choline as choline bitartrate (free choline); (ii) 600 mg choline as phosphatidylcholine; or (iii) no choline control in a random order. Blood and urine samples were collected at baseline and throughout the 6-h study period; a one-time stool sample was collected at baseline. Results Compared to no choline and phosphatidylcholine, free choline yielded 295% higher plasma TMAO (P = 0.002) and 250% higher urinary TMAO (P = 0.01), with no difference in TMAO response between phosphatidylcholine and no choline. High-TMAO producers (those with ≥40% increase in urinary TMAO response to free choline) had significantly different beta-diversity measures (unweighted UniFrac; PERMANOVA P = 0.01) compared to low-TMAO producers (those with &lt;40% increase in TMAO response) but showed no difference in alpha-diversity. Analysis of Composition of Microbiomes (ANCOM) revealed that high-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae (in phylum Firmicutes) compared to low-TMAO producers (P &lt; 0.05 with the strength of the ANCOM test W = 11 and W = 8, respectively). Conclusions Given that the majority of choline in food is in the form of phosphatidylcholine, the absence of TMAO elevation with phosphatidylcholine counters arguments that dietary choline should be avoided for TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiota composition may be a more appropriate strategy to reduce risk of cardiovascular disease. Funding Sources This research was supported by the Utah Agricultural Experiment Station Seed Grants Program.

scholarly journals Gut microbiota modulation induced by Zika virus infection in immunocompetent mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rafael Corrêa ◽  
Igor de Oliveira Santos ◽  
Heloísa Antoniella Braz-de-Melo ◽  
Lívia Pimentel de Sant’Ana ◽  
Raquel das Neves Almeida ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Zika Virus ◽  
Hypervariable Region ◽  
Microbiota Composition ◽  
Colon Tissue ◽  
Zikv Infection ◽  
Immunological Responses ◽  
Immunocompetent Mice ◽  
Gut Microbiota Composition

AbstractGut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.

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

2019 ◽  
Vol 110 (2) ◽  
pp. 316-329 ◽  
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.

scholarly journals 2581. An Invertebrate Model to Study Gut Microbiome Dysbiosis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S896-S897
Author(s):  
Faris S Alnezary ◽  
Tasnuva Rashid ◽  
Khurshida Begum ◽  
Travis J Carlson ◽  
Anne J Gonzales-Luna ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Galleria Mellonella ◽  
Nigella Sativa ◽  
Gut Contents ◽  
In Vivo Model ◽  
Microbiota Composition ◽  
Invertebrate Model ◽  
Gut Microbiota Composition

Abstract Background Antimicrobials disrupt the gut microbiota by reducing gut microbiome diversity and quantity. Galleria mellonella provides an invertebrate model that is inexpensive, easy to maintain, and does not require specialized equipment. This study investigated the feasibility of using G. mellonella as an in vivo model to evaluate the effect of different antimicrobials on gut microbiota. Methods To determine baseline gut microbiota composition, the gut contents of G. mellonella were extracted and genomic DNA underwent shotgun meta-genomic sequencing. To determine the effect of infection and antibiotic use, 30 larvae were injected (left proleg) with ~1 × 105 colony-forming unit (cfu) of methicillin-resistant Staphylococcus aureus (MRSA) and were randomized 1:1:1 to treatment with vancomycin (20 mg/kg) or a natural antimicrobial (Nigella sativa seed oil, 70 mg/kg; NS oil), or a combination. The larvae were kept at 37°C post-infection and monitored daily for 72 hours for activity, extent of cocoon formation/growth, melanization, and survival. Two larvae from each group were randomly selected and homogenized with PBS as controls. After 24 hours of incubation, gut contents were extracted and plated for MRSA and Enterococcus cfu counts. Results Metagenomics analysis showed the gut microbiota composition of G. mellonella larvae was dominated by a subset of closely-related Enterococcus species. After 24 hours of exposure, mean Enterococcus counts were 4 × 103 cfu in the vancomycin arm and 6.2 × 104 cfu in the NS oil arm. Mean MRSA counts were 3.3 × 105 cfu in vancomycin arm and 1.5 × 104 cfu in NS oil arm. The combination of vancomycin and NS oil had higher Enterococcus counts than the vancomycin alone arm (6.3 × 104 cfu vs. 4 × 103 cfu, respectively), suggesting that NS oil may have a role in protecting the gut microbiota. Conclusion This study provides preliminary evidence to support the potential use of G. mellonella to assess the in vivo effect of a natural and synthetic antimicrobial on the gut microbiota. Disclosures All authors: No reported disclosures.

scholarly journals Liver-specific knockdown of ANGPTL8 alters the structure of the gut microbiota in mice

2020 ◽  
Vol 70 (1) ◽  
Author(s):  
Yinlong Cheng ◽  
Yining Li ◽  
Yonghong Xiong ◽  
Yixin Zou ◽  
Siyu Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Shannon Index ◽  
Microbiota Composition ◽  
Functional Prediction ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Significant Difference ◽  
And Function ◽  
Gut Microbiota Composition

Abstract Purpose To investigate the effect of liver-specific knockdown of ANGPTL8 on the structure of the gut microbiota. Methods We constructed mice with liver-specific ANGPTL8 knockdown by using an adeno-associated virus serotype 8 (AAV8) system harbouring an ANGPTL8 shRNA. We analysed the structure and function of the gut microbiome through pyrosequencing and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional prediction. Results Compared with controls, ANGPTL8 shRNA reduced the Simpson index and Shannon index (p < 0.01) of the gut microbiota in mice. At the phylum level, the sh-ANGPTL8 group showed a healthier gut microbiota composition than controls (Bacteroidetes: controls 67.52%, sh-ANGPTL8 80.75%; Firmicutes: controls 10.96%, sh-ANGPTL8 8.58%; Proteobacteria: controls 9.29%, sh-ANGPTL8 0.98%; F/B ratio: controls 0.16, sh-ANGPTL8 0.11). PCoA and UPGMA analysis revealed a significant difference in microbiota composition, while KEGG analysis revealed a significant difference in microbiota function between controls and the sh-ANGPTL8 group. Conclusion Our results revealed that inhibition of ANGPTL8 signalling altered the structure of the gut microbiome, which might further affect the metabolism of mice. We have thus identified ANGPTL8 as a novel hepatogenic hormone potentially involving the liver-gut axis and regulating the structure of the gut microbiota.

scholarly journals Microbiome transfer between IL-1RI-/- and wild-type mice during high or low-fat feeding alters metabolic tissue functionality but not glucose homeostasis.

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Jessica C. Ralston ◽  
Kathleen A.J. Mitchelson ◽  
Gina M. Lynch ◽  
Tam T.T. Tran ◽  
Conall R. Strain ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Homeostasis ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Microbiota Composition ◽  
Wild Type ◽  
Low Fat ◽  
Unifrac Distance ◽  
Gut Microbiota Composition

AbstractReduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.

scholarly journals Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Stool Samples ◽  
Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

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

Nutrients ◽  
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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