Longitudinal Reduction in Diversity of Maternal Gut Microbiota During Pregnancy Is Observed in Multiple Low-Resource Settings: Results From the Women First Trial.

Objective: To characterize the changes in gut microbiota during pregnancy and determine the effects of nutritional intervention on gut microbiota in women from sub-Saharan Africa (the Democratic Republic of the Congo, DRC), South Asia (India and Pakistan), and Central America (Guatemala). Methods: Pregnant women in the Women First (WF) Preconception Maternal Nutrition Trial were included in this analysis. Participants were randomized to receive a lipid-based micronutrient supplement either ≥3 months before pregnancy (Arm 1); started the same intervention late in the first trimester (Arm 2); or received no nutrition supplements besides those self-administered or prescribed through local health services (Arm 3). Stool and blood samples were collected during the first and third trimesters. Findings presented here include fecal 16S rRNA gene-based profiling and systemic and intestinal inflammatory biomarkers, including alpha (1)-acid glycoprotein (AGP), C-reactive protein (CRP), fecal myeloperoxidase (MPO), and calprotectin. Results: Stool samples were collected from 640 women (DRC, n = 157; India, n = 102; Guatemala, n = 276; and Pakistan, n = 105). Gut microbial community structure did not differ by intervention arm but changed significantly during pregnancy. Richness, a measure of alpha-diversity, decreased over pregnancy. Community composition (beta-diversity) also showed a significant change from first to third trimester in all four sites. Of the top 10 most abundant genera, unclassified Lachnospiraceae significantly decreased in Guatemala and unclassified Ruminococcaceae significantly decreased in Guatemala and DRC. The change in the overall community structure at the genus level was associated with a decrease in the abundances of certain genera with low heterogeneity among the four sites. Intervention arms were not significantly associated with inflammatory biomarkers at 12 or 34 weeks. AGP significantly decreased from 12 to 34 weeks of pregnancy, whereas CRP, MPO, and calprotectin did not significantly change over time. None of these biomarkers were significantly associated with the gut microbiota diversity. Conclusion: The longitudinal reduction of individual genera (both commensals and potential pathogens) and alpha-diversity among all sites were consistent and suggested that the effect of pregnancy on the maternal microbiota overrides other influencing factors, such as nutrition intervention, geographical location, diet, race, and other demographical variables.

Probiotic supplements prevented oxonic acid-induced hyperuricemia and renal damage.

Hyperuricemia is highly prevalent and especially common in subjects with metabolic, cardiovascular and renal diseases. In chronic kidney disease, hyperuricemia is extremely common, and uric acid (UA) excretion relies on gut uricolysis by gut microbiota. Current therapy for lowering serum UA includes drugs that may produce undesired secondary effects. Therefore, this pilot study was designed to evaluate the potential of two probiotic supplements to reduce systemic uric acid concentrations. Secondary objectives were to assess whether the hypouricemic effect related to a therapeutic benefit on the hyperuricemia-induced renal damage and hypertension. Analysis of fecal microbiota was also performed. Groups of 6 rats each were followed for 5 weeks and allocated in the following treatment groups: C = Control; HU-ND = Oxonic acid-induced hyperuricemia (HU) +regular diet; HU-P = HU+placebo; HU-F1 = HU+ probiotics formula 1 and HU-F2 = HU+ probiotics formula 2. We confirmed that oxonic acid-induced hyperuricemia produced hypertension and renal functional and structural changes, along with modest changes in the overall composition of fecal microbiota. Both probiotic-containing diets prevented HU, elevated UA urinary excretion and intrarenal UA accumulation induced by oxonic acid. The hypouricemic effect conferred by probiotic supplementation also prevented the renal changes and hypertension caused by hyperuricemia. However, probiotic treatment did not restore the fecal microbiota. In conclusion, we demonstrated for the first time the ability of probiotics containing uricolytic bacteria to lower serum uric acid in hyperuricemic animals with beneficial consequences on blood pressure and renal disease. As probiotics supplements are innocuous for human health, we recommend clinical studies to test if probiotic supplements could benefit hyperuricemic individuals.

Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants.

Iron supplementation may have adverse health effects in infants, probably through manipulation of the gut microbiome. Previous research in low-resource settings have focused primarily on anemic infants. This was a double blind, randomized, controlled trial of home fortification comparing multiple micronutrient powder (MNP) with and without iron. Six-month-old, non- or mildly anemic, predominantly-breastfed Kenyan infants in a rural malaria-endemic area were randomized to consume: (1) MNP containing 12.5 mg iron (MNP+Fe, n = 13); (2) MNP containing no iron (MNP-Fe, n = 13); or (3) Placebo (CONTROL, n = 7), from 6-9 months of age. Fecal microbiota were profiled by high-throughput bacterial 16S rRNA gene sequencing. Markers of inflammation in serum and stool samples were also measured. At baseline, the most abundant phylum was Proteobacteria (37.6% of rRNA sequences). The proteobacterial genus Escherichia was the most abundant genus across all phyla (30.1% of sequences). At the end of the intervention, the relative abundance of Escherichia significantly decreased in MNP-Fe (-16.05 ± 6.9%, p = 0.05) and CONTROL (-19.75 ± 4.5%, p = 0.01), but not in the MNP+Fe group (-6.23 ± 9%, p = 0.41). The second most abundant genus at baseline was Bifidobacterium (17.3%), the relative abundance of which significantly decreased in MNP+Fe (-6.38 ± 2.5%, p = 0.02) and CONTROL (-8.05 ± 1.46%, p = 0.01), but not in MNP-Fe (-4.27 ± 5%, p = 0.4445). Clostridium increased in MNP-Fe only (1.9 ± 0.5%, p = 0.02). No significant differences were observed in inflammation markers, except for IL-8, which decreased in CONTROL. MNP fortification over three months in non- or mildly anemic Kenyan infants can potentially alter the gut microbiome. Consistent with previous research, addition of iron to the MNP may adversely affect the colonization of potential beneficial microbes and attenuate the decrease of potential pathogens.

Effect of Vitamin E With Therapeutic Iron Supplementation on Iron Repletion and Gut Microbiome in US Iron Deficient Infants and Toddlers.

BACKGROUND: Iron therapy induces inflammation, which could decrease iron absorption. Increased exposure of iron in the gut could also alter microbiome file. Providing antioxidants such as vitamin E with iron therapy has been associated with reduced oxidative potential. OBJECTIVE: The aim of the present study was to test the efficacy of adding vitamin E to therapeutic iron therapy on iron repletion, inflammation markers, and gut microbiome in iron-deficient infants and toddlers. DESIGN: This was a randomized, double-blind, control trial in which infants and toddlers (Denver, CO metro area) who were at risk of iron deficiency were screened. Eligible participants were randomized to receive iron therapy (6 mg ·â€Škg ·â€Šday) plus placebo (n = 22) or iron (6 mg ·â€Škg ·â€Šday) and vitamin E (18 mg/day, n = 14) for 8 weeks. Iron and inflammation status, and gut microbiome (16S sequencing) were analyzed in all participants before and after the treatment. RESULTS: After 8 weeks of treatment, average serum ferritin level returned to normal for both iron + placebo and iron + vitamin E groups at 33.3 ±â€Š20.2 and 33.5 ±â€Š21.5 µg/L, respectively. Serum vitamin E concentration increased in iron + vitamin E group. No change over time was observed regarding serum interleukin-4, tumor necrosis factor-α, or fecal calprotectin. The relative abundance of the genus Roseburia (phylum Firmicutes), a butyrate producer, increased in the Fe + E group (Δ1.3%, P < 0.01). Also at the genus level, the genus Escherichia decreased by 1.2% on average among all participants (effect of time P = 0.01). CONCLUSIONS: Using a therapeutic iron dose of 6 mg ·â€Škg ·â€Šday is effective in treating iron deficiency during an 8-week period, without inducing persistent inflammatory response. Changes of the gut microbiome raised the possibility that antioxidant therapy in conjunction with therapeutic iron supplementation could potentially improve microbial community profiles in the intestinal tract.

Evaluation of bacterial transmission to the paranasal sinuses through sinus irrigation.

BACKGROUND: Saline nasal irrigation is effective in the treatment of sinonasal disorders, including chronic rhinosinusitis (CRS). Despite bacterial contamination in rinse bottles and reports of infections from contaminated irrigation water, tap water is still used by ∼50% of irrigation users, raising a potential public health concern. This study aimed to determine whether bacteria from the water supply used in sinus irrigations colonizes the paranasal sinuses. METHODS: Samples were taken from the: (1) water used for irrigation, (2) faucet or container the water originated from, (3) rinse bottle, and (4) postoperative ethmoid cavity from 13 subjects with CRS. Microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to assess similarity in microbiota between samples, and genomic analysis was performed to assess clonality of cultured bacteria. RESULTS: Of 13 subjects, 6 used distilled water, 6 used tap water, and 1 used well water in this institutional review board (IRB)-approved observational study. Well-water had markedly more bacteria than tap or distilled water. There was a trend toward tap having more bacteria than distilled water. The sinus samples were notably dissimilar to the bottle, faucet, and irrigant (M-H 0.15, 0.09, and 0.18, respectively). There was no difference in postoperative microbiotas between distilled and tap water users. CONCLUSION: The current study suggests that irrigation plays little role in establishing the sinus microbiome. Although rinsing with tap water may never be formally recommended, these data are useful to counsel patients who prefer to do so in non-endemic areas if the municipal water supply is appropriately treated.