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

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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Differences in the Microbial Composition of Hemodialysis Patients Treated with and without β-Blockers

Journal of Personalized Medicine ◽

10.3390/jpm11030198 ◽

2021 ◽

Vol 11 (3) ◽

pp. 198

Author(s):

Yi-Ting Lin ◽

Ting-Yun Lin ◽

Szu-Chun Hung ◽

Po-Yu Liu ◽

Wei-Chun Hung ◽

...

Keyword(s):

Random Forest ◽

Gut Microbiota ◽

Hemodialysis Patients ◽

Microbiota Composition ◽

Microbial Composition ◽

Α Diversity ◽

Β Blocker ◽

Β Blockers ◽

The Impact ◽

Gut Microbiota Composition

β-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, β-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between β-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 β-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in β-blocker users with a distinct β-diversity (Bray–Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in β-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using β-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with β-blocker treatment. Our findings highlight the impact of β-blockers on the gut microbiota in hemodialysis patients.

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Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

European Heart Journal ◽

10.1093/ehjci/ehaa946.3823 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Roessler ◽

F Zimmermann ◽

D Schmidt ◽

U Escher ◽

A Jasina ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

Interindividual Variation ◽

Funding Source ◽

Microbial Composition ◽

Atorvastatin Treatment ◽

Qrt Pcr ◽

16S Rna ◽

Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

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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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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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Differences in the Microbial Composition of Hemodialysis Patients Treated With and Without β-Blockers

10.21203/rs.3.rs-36588/v1 ◽

2020 ◽

Author(s):

Yi-Ting Lin ◽

Ting-Yun Lin ◽

Szu-Chun Hung ◽

Po-Yu Liu ◽

Wei-Chun Hung ◽

...

Keyword(s):

Gut Microbiota ◽

Hemodialysis Patients ◽

Size Analysis ◽

Matched Cohort ◽

Microbial Composition ◽

Full Cohort ◽

Α Diversity ◽

Β Blocker ◽

Β Blockers ◽

The Impact

Abstract Background: β-blockers are commonly prescribed medications to treat cardiovascular disease and prevent sudden cardiac death during hemodialysis. Beyond the medication effects on the host, no study has investigated the impact of β-blocker on the gut microbiota in hemodialysis patients. Results: The β-blocker users had a higher proportion of diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, heart failure, cerebrovascular disease, and concurrent medications than non-users. After propensity score (PS) matching, there were no differences in comorbidities and concomitant medications. The α-diversity (Simpson index) increased in β-blocker users with a distinct β-diversity (Bray-Curtis Index) compared to non-users in the full cohort and PS-matched cohort. In the linear discriminative analysis effect size analysis and zero-inflated Gaussian fit model, there was a significant enrichment in the genus Flavonifractor in β-blocker users compared to non-users in the full cohort and PS-matched cohort; this was confirmed by random forest analysis. Conclusions: Hemodialysis patients using β-blocker used had a different gut microbiota composition compared to non-users, in particular, the Flavonifractor genus was significantly increased with β-blocker treatment. These findings highlight the significant impact of β-blockers on the gut microbiome in hemodialysis patients. Further research is warranted regarding the mechanisms and their clinical consequences.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz040.or23-08-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Edward Deehan ◽

Chen Yang ◽

Maria Elisa Perez-Munoz ◽

Khoi Nguyen ◽

Lucila Triador ◽

...

Keyword(s):

Gut Microbiota ◽

Microbiota Composition ◽

Double Blind ◽

Bifidobacterium Adolescentis ◽

Essential Information ◽

Α Diversity ◽

16S Rna ◽

Wide Range ◽

Resistant Starches ◽

Dose Dependent

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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Crosstalk of gut microbiota and serum/hippocampus metabolites in neurobehavioral impairments induced by oral zinc oxide nanoparticles exposure

10.21203/rs.3.rs-20829/v1 ◽

2020 ◽

Author(s):

jianjun Chen ◽

Shanshan Zhang ◽

Chang Chen ◽

Xuejun Jiang ◽

Jingfu Qiu ◽

...

Keyword(s):

Zinc Oxide ◽

Gut Microbiota ◽

Gut Microbiome ◽

Zinc Oxide Nanoparticles ◽

Oral Exposure ◽

Oxide Nanoparticles ◽

Rrna Gene ◽

Environmental Toxicants ◽

Microbial Composition ◽

Α Diversity

Abstract Background Gut microbiome can be readily influenced by external factors, such as diet, antibiotic, bacterial/viral infection and environmental toxicants. Gut microbiota-mediated effects of engineered nanomaterials as such become the new frontiers in nanotoxicology. Methods An integrated approach combining 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to determine the potential mechanistic pathway by which disturbed gut microbiota induced by ZnONPs might modulate host physiology and neurobehavior. Results Herein, we showed oral exposure to zinc oxide nanoparticles (ZnONPs), one typical kinds of nanomaterials used widely in the food industry, could cause the neurobehavioral dysfunctions in mice, manifested by spatial learning and memory deficits and locomotor activity inhibition. Our mechanistic results elucidated that ZnONPs exposure led to a marked disturbance of gut microbial composition but did not alter the microbiome α-diversity indexes. We also provided new evidence that neurobehavioral impairments induced by ZnONPs was closely associated with perturbation in the gut microbiota composition that were both specific to changes of neurobehavior-related genes (such as Bdnf and Dlg4 ) and correlated with serum and hippocampal metabolic disorders. Our data further identified a unique metabolite [DG(15:0/0:0/22:4n6)] that linked the relationships among gut microbiota, metabolites and neurobehavior-related genes. Conclusions ZnONPs exposure not only alters the gut microbiome community but also substantially disturbs its metabolic profiles, and therefore leading to neurobehavioral impairments vi gut-brain axis. These findings will provide a novel view for understanding the ZnONPs neurotoxicity through gut-brain axis and may lead to new potential prevention and treatment strategies.

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P0272COMPARATIVE GUT MICROBIOME DIFFERENCES BETWEEN FERRIC CITRATE AND CALCIUM CARBONATE PHOSPHATE BINDER TREATMENT IN HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0272 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Ping-Hsun Wu ◽

Yi-Ting Lin ◽

Po-Yu Liu ◽

Mei-Chuan Kuo ◽

Yi wen Chiu

Keyword(s):

Calcium Carbonate ◽

Gut Microbiome ◽

Phosphate Binder ◽

Hemodialysis Patients ◽

Ferric Citrate ◽

Phosphate Binders ◽

Uremic Toxin ◽

Phosphate Binding ◽

Microbial Composition ◽

Linear Discriminant

Abstract Background and Aims Gut microbiome alteration increases uremic toxin levels inducing chronic inflammation and leading morbidity and mortality in patients with chronic kidney disease. Phosphate-binding agents may potentially change the composition of the gut microbiota. However, the limited clinical study investigates the microbiome difference between iron-containing and calcium-containing phosphate binders. The aim of this study was to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. Method The stool microbiota was investigated in hemodialysis patients with ferric citrate used (n=8) and calcium carbonate used (n=46) by 16S rRNA next-generation gene sequencing profiling. The altered microbiota between two different phosphate binders was analyzed. Differences in the microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Results Hemodialysis patients with calcium carbonate used revealed significantly reduced microbial species diversity (Shannon index and Simpson index) and increased microbial dysbiosis index compared with ferric citrate users. Compared to patients taking calcium carbonate, a distinct microbial community structure in patients taking ferric citrate, with an increased abundance of Bacteroidetes phylum and decreased abundance of phylum Firmicutes. In comparison between two phosphate binder users, members of the order Lactobacillales were prominent in calcium carbonate therapy, including family Streptococcaceae and genus Streptococcus. In contrast, taxa of the genus Ruminococcaceae, Flavonifractor, and Cronobacter were enriched in ferric citrate phosphate binder users. Conclusion The fecal microbiota was richer and more diverse in the ferric citrate group than in the calcium carbonate group. Hemodialysis patients with ferric citrate used were associated with differences in the gut microbiome composition compared to calcium carbonate users.

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Monitoring the variation in the gut microbiota of captive woolly monkeys related to changes in diet during a reintroduction process

Scientific Reports ◽

10.1038/s41598-021-85990-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Camilo Quiroga-González ◽

Luis Alberto Chica Cardenas ◽

Mónica Ramírez ◽

Alejandro Reyes ◽

Camila González ◽

...

Keyword(s):

Gut Microbiota ◽

Site Conditions ◽

Microbiota Composition ◽

Microbial Composition ◽

Bacterial Composition ◽

Diet Diversity ◽

Woolly Monkeys ◽

The Moment ◽

Positive Effect ◽

Lagothrix Lagothricha

AbstractMicrobiome is known to play an important role in the health of organisms and different factors such as diet have been associated with modifications in microbial communities. Differences in the microbiota composition of wild and captive animals has been evaluated; however, variation during a reintroduction process in primates has never been reported. Our aim was to identify changes in the bacterial composition of three individuals of reintroduced woolly monkeys (Lagothrix lagothricha) and the variables associated with such changes. Fecal samples were collected and the V4 region of the 16S rRNA gene was sequenced to determine gut microbial composition and functionality. Individual samples from released individuals showed a higher microbial diversity after being released compared to before liberation, associated with changes in their diet. Beta diversity and functionality analysis showed separation of samples from released and captive conditions and the major factor of variation was the moment of liberation. This study shows that intestinal microbiota varies depending on site conditions and is mainly associated with diet diversity. The intake of food from wild origin by released primates may promote a positive effect on gut microbiota, improving health, and potentially increasing success in reintroduction processes.

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Gut microbiota modulation induced by Zika virus infection in immunocompetent mice

Scientific Reports ◽

10.1038/s41598-020-80893-y ◽

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.

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