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The Effect of Oral Iron Supplementation on Gut Microbial Composition: a Secondary Analysis of a Double-Blind, Randomized Controlled Trial among Cambodian Women of Reproductive Age.
Finlayson-Trick, E, Nearing, J, Fischer, JA, Ma, Y, Wang, S, Krouen, H, Goldfarb, DM, Karakochuk, CD
Microbiology spectrum. 2023;11(3):e0527322
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Iron supplementation is recommended for all women of reproductive age in Cambodia, where anaemia has a high prevalence. The gut microbiome contains iron-dependent bacteria with the potential to cause intestinal disease (enteropathogens). The aim of this study was to examine changes in the gut microbiome following 12 weeks of daily supplementation of either ferrous sulfate or ferrous bisglycinate in non-pregnant Cambodian women of reproductive age. This study was nested within a larger randomised controlled trial of oral iron supplementation that included 480 non-pregnant Cambodian women. The participants were randomised at a 1:1:1 allocation ratio to either ferrous sulfate, ferrous bisglycinate, or placebo. Results showed that daily iron supplementation did not significantly affect gut bacterial diversity. However, iron supplementation, in the form of ferrous bisglycinate, increases the relative abundance of Enterobacteriaceae. Authors conclude that their findings can facilitate future research that may inform evidence-based global practice and policy.
Abstract
The World Health Organization recommends untargeted iron supplementation for women of reproductive age (WRA) in countries where anemia prevalence is greater than 40%, such as Cambodia. Iron supplements, however, often have poor bioavailability, so the majority remains unabsorbed in the colon. The gut houses many iron-dependent bacterial enteropathogens; thus, providing iron to individuals may be more harmful than helpful. We examined the effects of two oral iron supplements with differing bioavailability on the gut microbiomes in Cambodian WRA. This study is a secondary analysis of a double-blind, randomized controlled trial of oral iron supplementation in Cambodian WRA. For 12 weeks, participants received ferrous sulfate, ferrous bisglycinate, or placebo. Participants provided stool samples at baseline and 12 weeks. A subset of stool samples (n = 172), representing the three groups, were randomly selected for gut microbial analysis by 16S rRNA gene sequencing and targeted real-time PCR (qPCR). At baseline, 1% of women had iron-deficiency anemia. The most abundant gut phyla were Bacteroidota (45.7%) and Firmicutes (42.1%). Iron supplementation did not alter gut microbial diversity. Ferrous bisglycinate increased the relative abundance of Enterobacteriaceae, and there was a trend towards an increase in the relative abundance of Escherichia-Shigella. qPCR detected an increase in the enteropathogenic Escherichia coli (EPEC) virulence gene, bfpA, in the group that received ferrous sulfate. Thus, iron supplementation did not affect overall gut bacterial diversity in predominantly iron-replete Cambodian WRA, however, evidence does suggest an increase in relative abundance within the broad family Enterobacteriaceae associated with ferrous bisglycinate use. IMPORTANCE To the best of our knowledge, this is the first published study to characterize the effects of oral iron supplementation on the gut microbiomes of Cambodian WRA. Our study found that iron supplementation with ferrous bisglycinate increases the relative abundance of Enterobacteriaceae, which is a family of bacteria that includes many Gram-negative enteric pathogens like Salmonella, Shigella, and Escherichia coli. Using qPCR for additional analysis, we were able to detect genes associated with enteropathogenic E. coli, a type of diarrheagenic E. coli known to be present around the world, including water systems in Cambodia. The current WHO guidelines recommend blanket (untargeted) iron supplementation for Cambodian WRA despite a lack of studies in this population examining iron's effect on the gut microbiome. This study can facilitate future research that may inform evidence-based global practice and policy.
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The Short-Term Variation of Human Gut Mycobiome in Response to Dietary Intervention of Different Macronutrient Distributions.
Tian, Y, Gou, W, Ma, Y, Shuai, M, Liang, X, Fu, Y, Zheng, JS
Nutrients. 2023;15(9)
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The human gut is inhabited by a diverse and complex community of microbes, such as bacteria, viruses, and fungi, which are critical in maintaining human health. Gut mycobiome is less diverse and abundant than bacteria in the gut, which comprises approximately 0.1% of the total gut microbes and inhabits symbiotically with bacteria as a commensal in the human gut. The aim of this study was to explore short-term gut mycobiome variations in response to a high-carbohydrate, low-fat (HC) diet and a low-carbohydrate, high-fat (LC) diet. This study was a cross-over N-of-1 feeding trial among 30 participants over 72 days (WE-MACNUTR). A total of 28 participants were included in the final analysis. Results showed that the HC diet, but not the LC diet, may increase the fungal alpha diversity at the populational level. Both dietary interventions may affect the gut fungal community structure (i.e., beta diversity). Furthermore, the dietary environment influenced the relationship between gut mycobiome and glycaemic phenotypes. Authors concluded that their findings provide novel evidence on how the gut mycobiome structure and composition change in response to the HC and LC dietary interventions and reveals diet-specific changes in the fungal genera.
Abstract
While the human gut is home to a complex and diverse community of microbes, including bacteria and fungi, research on the gut microbiome has largely focused on bacteria, with relatively little attention given to the gut mycobiome. This study aims to investigate how diets with different dietary macronutrient distributions impact the gut mycobiome. We investigated gut mycobiome response to high-carbohydrate, low-fat (HC) and low-carbohydrate high-fat (LC) diet interventions based on a series of 72-day feeding-based n-of-1 clinical trials. A total of 30 participants were enrolled and underwent three sets of HC and LC dietary interventions in a randomized sequence. Each set lasted for 24 days with a 6-day washout period between dietary interventions. We collected and analyzed the fungal composition of 317 stool samples before and after each intervention period. To account for intra-individual variation across the three sets, we averaged the mycobiome data from the repeated sets for analysis. Of the 30 participants, 28 (aged 22-34 years) completed the entire intervention. Our results revealed a significant increase in gut fungal alpha diversity (p < 0.05) and significant changes in fungal composition (beta diversity, p < 0.05) after the HC dietary intervention. Specifically, we observed the enrichment of five fungal genera (Pleurotus, Kazachstania, Auricularia, Paraphaeosphaeria, Ustilaginaceae sp.; FDR < 0.052) and depletion of one fungal genus (Blumeria; FDR = 0.03) after the HC intervention. After the LC dietary intervention, one fungal genus was enriched (Ustilaginaceae sp.; FDR = 0.003), and five fungal genera were depleted (Blumeria, Agaricomycetes spp., Malassezia, Rhizopus, and Penicillium; FDR < 0.1). This study provides novel evidence on how the gut mycobiome structure and composition change in response to the HC and LC dietary interventions and reveals diet-specific changes in the fungal genera.
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The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.
Brakedal, B, Dölle, C, Riemer, F, Ma, Y, Nido, GS, Skeie, GO, Craven, AR, Schwarzlmüller, T, Brekke, N, Diab, J, et al
Cell metabolism. 2022;34(3):396-407.e6
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Parkinson’s disease (PD) is a major cause of death and disability, and current treatments can provide partial symptomatic relief, mainly for motor symptoms but make no substantial impact on disease progression. A growing body of evidence supports that boosting cellular levels of nicotinamide adenine dinucleotide (NAD) may confer neuroprotective effects in both healthy aging and neurodegeneration. The primary aim of this study was to assess penetration and metabolic responses of the brain to nicotinamide riboside (NR) supplementation in patients with PD. This study is a double-blinded, randomised, placebo-controlled phase I study of NR in newly diagnosed PD patients, naïve to dopaminergic therapy. Participants (n=30) where randomly assigned (1:1) to one of the two groups: NR group or placebo group. Results show that: - oral NR therapy increases brain NAD levels and impacts cerebral metabolism in PD. - supplementation with NR may target multiple processes implicated in the pathophysiology of the disease by upregulating the expression of genes involved in mitochondrial respiration, oxidative damage response, lysosomal and proteasomal function and downregulating inflammatory cytokines in the central nervous system. Authors conclude that NR can be a potential neuroprotective agent against PD. However, further investigation in a larger trial is required to warrant these findings.
Abstract
We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.
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Effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury.
Li, X, Liu, Y, Guo, X, Ma, Y, Zhang, H, Liang, H
European journal of clinical nutrition. 2021;75(8):1227-1236
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Alcoholic liver disease (ALD) is a series of liver diseases caused by long-term heavy drinking. Lipid metabolism disorder often occurs in people with alcoholic liver injury. Treatment is mainly a combination of alcohol abstinence, improving nutrition, treating the liver injury, and preventing or reversing the progress of liver fibrosis or promoting liver regeneration. The aim of this study was to investigate the effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury. This study was a randomised, double-blind, placebo-controlled trial. A total of 181 ALD patients were recruited and randomly assigned to one of the three groups; low-dose group, high-dose group and positive control group (+ there was another group of 20 healthy people which served as normal control group). Results showed disorder of lipid metabolism, intestinal flora imbalance and inflammation in patients with alcoholic liver injury. Furthermore, after supplementation of Lactobacillus casei, there was a significant increase in the amount of Lactobacillus and Bifidobacterium. Authors conclude that Lactobacillus casei supplementation can improve lipid metabolism and regulate intestinal flora disorders in patients with alcoholic liver injury.
Abstract
BACKGROUND The present study aims to investigate the effect of Lactobacillus casei on lipid metabolism and intestinal microflora in patients with alcoholic liver injury. METHODS In a double-blind randomized controlled trial, 158 recruited alcoholic liver injury patients were randomized to three treatments for 60 days: low-dose group (LP, n = 58, 100 ml of Lactobacillus casei strain Shirota (LcS)), high-dose group (HP, n = 54, 200 ml of LcS), and positive control group (PC, n = 46, 100 ml of special drinks without active Lactobacillus casei). Another group of 20 healthy people was served as normal control group (NC). RESULTS The serum levels of TG and LDLC in the HP group were significantly decreased by 26.56% and 23.83%, respectively than those in the PC group (P < 0.05). After supplementation of Lactobacillus casei, there was a significant increase in the amount of Lactobacillus and Bifidobacterium when compared with the PC group (P < 0.05). CONCLUSIONS Supplementation of Lactobacillus casei can improve lipid metabolism and regulate intestinal flora disorders in patients with alcoholic liver injury.
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Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study.
Wang, S, Ma, P, Zhang, S, Song, S, Wang, Z, Ma, Y, Xu, J, Wu, F, Duan, L, Yin, Z, et al
Diabetologia. 2020;63(10):2102-2111
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Hyperglycaemia was a risk factor for mortality from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is an independent risk factor for lower respiratory tract infection and poor prognosis. The aim of this retrospective study of 605 patients without previously diagnosed diabetes was to examine the association between fasting blood glucose (FBG) on admission and the 28-day in hospital mortality of COVID-19 patients. Patients with a FBG level of 7.0mmol/l or over had more than double the risk of dying than those with a level of 6.0mmol/l or less. Other risk factors for mortality included age, being male, and severity of pneumonia at admission. Compared with patients whose FBG was 6.0mmol/l or lower at admission, patients with FBG of 7.0 mmol/l and above had a 3.99 times higher risk of in-hospital complications, whilst those with FBG of 6.1–6.9 mmol/l had a 2.61 times higher risk of complications. The authors conclude that glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes.
Abstract
AIMS/HYPOTHESIS Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1-2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3-4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1-6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. Graphical abstract.