Gut microbiome in hemodialysis patients treated with calcium acetate or treated with sucroferric oxyhydroxide: a pilot study

Abstract Purpose It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. Methods Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. Results Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different (p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. Conclusion These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients.

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Calcium Acetate versus Calcium Carbonate as Phosphate Binders in Hemodialysis Patients

Nephron ◽

10.1159/000186802 ◽

1992 ◽

Vol 60 (4) ◽

pp. 423-427 ◽

Cited By ~ 36

Author(s):

F. Caravaca ◽

I. Santos ◽

J.J. Cubero ◽

J.F. Esparrago ◽

M. Arrobas ◽

...

Keyword(s):

Calcium Carbonate ◽

Hemodialysis Patients ◽

Calcium Acetate ◽

Phosphate Binders

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Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants

Scientific Reports ◽

10.1038/s41598-021-80982-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jordan T. Russell ◽

J. Lauren Ruoss ◽

Diomel de la Cruz ◽

Nan Li ◽

Catalina Bazacliu ◽

...

Keyword(s):

Preterm Infants ◽

Gut Microbiome ◽

Antibiotic Use ◽

Intestinal Microbiome ◽

Preterm Neonates ◽

Gamma Aminobutyric Acid ◽

Microbiome Diversity ◽

Infant Gut Microbiome ◽

Stool Samples ◽

To Receive

AbstractAntibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.Trial Registration This project is registered at clinicaltrials.gov under the name “Antibiotic ‘Dysbiosis’ in Preterm Infants” with trial number NCT02784821.

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Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment: a randomized trial of preterm infants

10.1101/2020.04.20.052142 ◽

2020 ◽

Cited By ~ 3

Author(s):

Jordan T. Russell ◽

J. Lauren Ruoss ◽

Diomel de la Cruz ◽

Nan Li ◽

Catalina Bazacliu ◽

...

Keyword(s):

Gut Microbiome ◽

Antibiotic Use ◽

Intestinal Microbiome ◽

Preterm Neonates ◽

Gamma Aminobutyric Acid ◽

Immune Markers ◽

Microbiome Diversity ◽

Infant Gut Microbiome ◽

Stool Samples ◽

To Receive

AbstractAntibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the Routine Early Antibiotic use in SymptOmatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 hours after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.

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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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Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease

Microorganisms ◽

10.3390/microorganisms8122040 ◽

2020 ◽

Vol 8 (12) ◽

pp. 2040

Author(s):

Ping-Hsun Wu ◽

Po-Yu Liu ◽

Yi-Wen Chiu ◽

Wei-Chun Hung ◽

Yi-Ting Lin ◽

...

Keyword(s):

Calcium Carbonate ◽

Kidney Disease ◽

Gut Microbiome ◽

Phosphate Binder ◽

Hemodialysis Patients ◽

Ferric Citrate ◽

Phosphate Binders ◽

Rrna Gene ◽

Phosphate Binding ◽

Linear Discriminant

Gut dysbiosis in patients with chronic kidney disease (CKD) may induce chronic inflammation and increase morbidity. Phosphate-binding agents, generally used in patients with CKD, may potentially change the composition of the gut microbiota. This study aimed to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. The stool microbiota was investigated in hemodialysis patients treated with ferric citrate (n = 8) and calcium carbonate (n = 46) using 16S rRNA gene amplicon sequencing profiling using linear discriminant analysis of effect size. Further predictive functional profiling of microbial communities was obtained with Tax4Fun in R. Hemodialysis patients treated with calcium carbonate had a significantly reduced microbial species diversity (Shannon index and Simpson index) and an increased microbial alteration ratio compared with patients treated with ferric citrate. A distinct microbial community structure was found in patients treated with ferric citrate, with an increased abundance of the Bacteroidetes phylum and a decreased abundance of the phylum Firmicutes. Members of the order Lactobacillales were enriched in patients treated with calcium carbonate, whereas taxa of the genera Ruminococcaceae UCG-004, Flavonifractor, and Cronobacter were enriched in patients treated with ferric citrate phosphate binder. In conclusion, Ferric citrate therapy results in a more diverse microbiome community compared to calcium carbonate therapy in hemodialysis patients with phosphate binder treatment. The gut microbiome reflects the phosphate binder choice in hemodialysis patients, further affecting the physiological environment in the gastrointestinal tract.

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Transient Effect of Infant Formula Supplementation on the Intestinal Microbiota

Nutrients ◽

10.3390/nu13030807 ◽

2021 ◽

Vol 13 (3) ◽

pp. 807

Author(s):

Ning Chin ◽

Gema Méndez-Lagares ◽

Diana H. Taft ◽

Victoria Laleau ◽

Hung Kieu ◽

...

Keyword(s):

16S Rrna ◽

Gut Microbiome ◽

Bacterial Species ◽

Bifidobacterium Longum ◽

The United States ◽

16S Rrna Sequencing ◽

T Cell Subsets ◽

Rrna Sequencing ◽

Stool Samples ◽

The Impact

Breastfeeding is the gold standard for feeding infants because of its long-term benefits to health and development, but most infants in the United States are not exclusively breastfed in the first six months. We enrolled 24 infants who were either exclusively breastfed or supplemented with formula by the age of one month. We collected diet information, stool samples for evaluation of microbiotas by 16S rRNA sequencing, and blood samples for assessment of immune development by flow cytometry from birth to 6 months of age. We further typed the Bifidobacterium strains in stool samples whose 16S rRNA sequencing showed the presence of Bifidobacteriaceae. Supplementation with formula during breastfeeding transiently changed the composition of the gut microbiome, but the impact dissipated by six months of age. For example, Bifidobacterium longum, a bacterial species highly correlated with human milk consumption, was found to be significantly different only at 1 month of age but not at later time points. No immunologic differences were found to be associated with supplementation, including the development of T-cell subsets, B cells, or monocytes. These data suggest that early formula supplementation, given in addition to breast milk, has minimal lasting impact on the gut microbiome or immunity.

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Implementation and effectiveness of an intensive education program on phosphate control among hemodialysis patients: a non-randomized, single-arm, single-center trial

BMC Nephrology ◽

10.1186/s12882-021-02441-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jinmei Yin ◽

Jun Yin ◽

Rongli Lian ◽

Peiqiu Li ◽

Jing Zheng

Keyword(s):

Education Program ◽

Hemodialysis Patients ◽

Serum Phosphorus ◽

Phosphate Binders ◽

Maintenance Hemodialysis ◽

Single Center ◽

Clinical Trial Registry ◽

Before And After ◽

Intensive Education ◽

Phosphate Control

Abstract Background Hyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients’ adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients. Objective To develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program. Design A non-randomized, single-arm, single-center trial lasting for 6 months. Setting This program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China. Participants Patients on maintenance hemodialysis with hyperphosphatemia. Methods An intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled percentage of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed. Results The proportion of controlled serum phosphorus was significantly increased from 43.5 to 54.9% (P<0.001). The scores on the knowledge of phosphate control were improved significantly from 59.0 ± 18.9 to 80.6 ± 12.4 (P < 0.001). The proportion of high adherence to phosphate binders was increased dramatically from 21.9 to 44.5% (P < 0.001). Conclusion The intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients. Trial registration Chinese Clinical Trial Registry, ChiCTR2100042017. Retrospectively registered January 12th, 2021.

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Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽

10.3390/life11030246 ◽

2021 ◽

Vol 11 (3) ◽

pp. 246

Author(s):

Felix C.F. Schmitt ◽

Martin Schneider ◽

William Mathejczyk ◽

Markus A. Weigand ◽

Jane C. Figueiredo ◽

...

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Gut Microbiota ◽

Gut Microbiome ◽

Tumor Resection ◽

Microbial Composition ◽

Colorectal Cancer Surgery ◽

Long Term Changes ◽

Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

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A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants

BMC Microbiology ◽

10.1186/s12866-021-02230-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Christophe Lay ◽

Collins Wenhan Chu ◽

Rikky Wenang Purbojati ◽

Enzo Acerbi ◽

Daniela I. Drautz-Moses ◽

...

Keyword(s):

Risk Factor ◽

Gut Microbiome ◽

Reference Group ◽

Mode Of Delivery ◽

Controlled Study ◽

Double Blind ◽

Lipopolysaccharide Biosynthesis ◽

Infant Gut Microbiome ◽

Stool Samples ◽

The Impact

Abstract Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838) on 4th April 2011.

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Phosphate Control: The Next Frontier in Dialysis Cardiovascular Mortality

Cardiorenal Medicine ◽

10.1159/000516286 ◽

2021 ◽

pp. 1-10

Author(s):

Peter A. McCullough

Keyword(s):

Calcium Acetate ◽

Paracellular Pathway ◽

Ferric Citrate ◽

Morbidity And Mortality ◽

Phosphate Binders ◽

Phosphate Absorption ◽

Phosphate Retention ◽

Sevelamer Carbonate ◽

Prescribing Information ◽

Phosphate Control

Background: Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD) on dialysis. Mortality rates are still unacceptably high even though they have fallen in the past 2 decades. Hyperphosphatemia (elevated serum phosphate levels) is seen in almost all patients with advanced CKD and is by far the largest remaining modifiable contributor to CKD mortality. Summary: Phosphate retention drives multiple physiological mechanisms linked to increased risk of CVD. Fibroblast growth factor 23 and parathyroid hormone (PTH) levels, both of which have been suggested to have direct pathogenic CV effects, increase in response to phosphate retention. Phosphate, calcium, and PTH levels are linked in a progressively worsening cycle. Maladaptive upregulation of phosphate absorption is also likely to occur further exacerbating hyperphosphatemia. Even higher phosphate levels within the normal range may be a risk factor for vascular calcification and, thus, CV morbidity and mortality. A greater degree of phosphate control is important to reduce the risk of CV morbidity and mortality. Improved phosphate control and regular monitoring of phosphate levels are guideline-recommended, established clinical practices. There are several challenges with the current phosphate management approaches in patients with CKD on dialysis. Dietary restriction of phosphate and thrice-weekly dialysis alone are insufficient/unreliable to reduce phosphate to <5.5 mg/dL. Even with the addition of phosphate binders, the only pharmacological treatment currently indicated for hyperphosphatemia, the majority of patients are unable to achieve and maintain phosphate levels <5.5 mg/dL (or more normal levels) [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information), 2011, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information), 2020, RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Phosphate binders do not target the primary pathway of phosphate absorption (paracellular), have limited binding capacity, and bind nonspecifically [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information). 2013, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information) 2020]. Key Messages: Despite current phosphate management strategies, most patients on dialysis are unable to consistently achieve target phosphate levels, indicating a need for therapeutic innovations [RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Given a growing evidence base that the dominant mechanism of phosphate absorption is the intestinal paracellular pathway, new therapies are investigating ways to reduce phosphate levels by blocking absorption through the paracellular pathway.

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