Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.

Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. Surprisingly, we also observed intradonor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the antibacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the antibacterial BrmIgA reactivity displays interindividual heterogeneity but intraindividual stability. These findings have important implications for how breast milk shapes the development of the preterm infant microbiota and protects against necrotizing enterocolitis.

Understanding the Burden of Kidney Failure in Trinidad and Tobago: A Review of the Epidemiological Data From a Regional Center.

Objective The aim of this study was to determine the incidence of new patients requiring renal replacement therapy and to gather data on sex, age, ethnicity, mortality, and causes of kidney failure in Trinidad and Tobago in comparison with the rest of the world. Method Electronic data were gathered for new patients initiating dialysis between January 1, 2016, and December 31, 2017, including the date of dialysis initiation, age, gender, ethnicity, diagnosis, dialysis access and modality, and outcome at three months and the end of the year. The data were analyzed using simple descriptive statistics via Microsoft Excel (Microsoft Corporation, Redmond, Washington, United States). Results Over a two-year period, 265 new patients underwent renal replacement therapy, of which 51.7% were 50-69 years of age, 53.9% were male, 46% were female, 67.9% were Afro-Trinidadian, and 38.1% had a combination of diabetes mellitus and hypertension as the cause of kidney failure. The incidence rates of treated end-stage renal disease (ESRD) globally in 2016 and 2017 were 306 and 224 per million population, respectively, and mortality for both years was 32% and 32.1%, respectively. Conclusion Our study showed that Trinidad and Tobago has one of the highest incidences of patients initiating renal replacement therapy and mortality rates.

Stability and heterogeneity in the anti-microbiota reactivity of human milk-derived Immunoglobulin A.

Immunoglobulin A (IgA) is secreted into breast milk and is critical to both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity, however heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. We also observed intra-donor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the anti-bacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the anti-bacterial BrmIgA reactivity displays inter-individual heterogeneity but intra-individual stability. These findings have important implications for how breast milk shapes the development of the infant microbiota and protects against Necrotizing Enterocolitis. Summary: We analyze the ability of breast milk-derived Immunoglobulin A (IgA) antibodies to bind the infant intestinal microbiota. We discover that each mother secretes into their breast milk a distinct set of IgA antibodies that are stably maintained over time.

Neonatal intermittent hypoxia, fish oil, and/or antioxidant supplementation on gut microbiota in neonatal rats.

BACKGROUND: Preterm infants frequently experience intermittent hypoxia (IH) episodes, rendering them susceptible to oxidative stress and gut dysbiosis. We tested the hypothesis that early supplementation with antioxidants and/or fish oil promotes gut biodiversity and mitigates IH-induced gut injury. METHODS: Newborn rats were exposed to neonatal IH from birth (P0) to P14 during which they received daily oral supplementation with: (1) coenzyme Q10 (CoQ10) in olive oil, (2) fish oil, (3) glutathione nanoparticles (nGSH), (4) CoQ10 + fish oil, or (5) olive oil (placebo control). Pups were placed in room air (RA) from P14 to P21 with no further treatment. RA controls were similarly treated. Stool samples were assessed for microbiota and terminal ileum for histopathology and morphometry, total antioxidant capacity, lipid peroxidation, and biomarkers of gut injury. RESULTS: Neonatal IH induced histopathologic changes consistent with necrotizing enterocolitis, which were associated with increased lipid peroxidation, toll-like receptor, transforming growth factor, and nuclear factor kappa B. Combination of CoQ10 + fish oil and nGSH were most effective for preserving gut integrity, reducing biomarkers of gut injury, and increasing commensal organisms. CONCLUSIONS: Combination of antioxidants and fish oil may confer synergistic benefits to mitigate IH-induced injury in the terminal ileum. IMPACT: Antioxidant and fish oil (PUFA) co-treatment was most beneficial for reducing neonatal IH-induced gut injury. The synergistic effects of antioxidant and fish oil is likely due to prevention of IH-induced ROS attack on lipids, thus preserving and augmenting its therapeutic benefits. Combination treatment was also effective for increasing the abundance of the non-pathogenic Firmicutes phylum, which is associated with a healthy gastrointestinal system of the newborn. Extremely low gestational age neonates who are at high risk for frequent, repetitive neonatal IH and oxidative stress-induced diseases may benefit from this combination therapy.

Antioxidants and/or fish oil reduce intermittent hypoxia-induced inflammation in the neonatal rat terminal ileum.

Intermittent hypoxia (IH) is associated with the pathogenesis of necrotizing enterocolitis (NEC). We tested the hypothesis that early supplementation with antioxidants and/or fish oil protects the terminal ileum from oxidative injury induced by neonatal IH. Newborn rats were exposed to neonatal IH from birth (P0) until P14 during which they received daily fish oil, coenzyme Q10 (CoQ10), glutathione nanoparticles (nGSH), fish oil + CoQ10, or olive oil. Pups were then placed in room air from P14 to P21 with no further supplementation. Terminal ileum was assessed for IH-induced injury and inflammatory biomarkers. Neonatal IH induced severe damage consistent with NEC, and was associated with oxidative stress and elevations in PGE2, PGF2α, TxB2, NOS-2 and TLR-4, effects that were ameliorated with nGSH and combination CoQ10+fish oil. Early postnatal supplementation with antioxidants and/or fish oil during neonatal IH may be favorable for preserving gut integrity and reducing oxidative injury.

Effects of omega 3 polyunsaturated fatty acids, antioxidants, and/or non-steroidal inflammatory drugs in the brain of neonatal rats exposed to intermittent hypoxia.

Preterm infants experience frequent arterial oxygen desaturations during oxygen therapy, or intermittent hypoxia (IH). Neonatal IH increases oxidative distress which contributes to neuroinflammation and brain injury. We tested the hypotheses that exposure to neonatal IH is detrimental to the immature brain and that early supplementation with antioxidants and/or omega 3 polyunsaturated fatty acids (n-3 PUFAs) combined with non-steroidal anti-inflammatory drugs (NSAIDs) is protective. Newborn rats were exposed to brief hypoxia (12% O2 ) during hyperoxia (50% O2 ) from the first day of life (P0) until P14 during which they received daily oral supplementation with antioxidants, namely coenzyme Q10 (CoQ10) or glutathione nanoparticles (nGSH), n-3 PUFAs and/or topical ocular ketorolac. Placebo controls received daily oral olive oil and topical ocular saline. Room air (RA) littermates remained in 21% O2 from birth to P21 with all treatments identical. At P14 animals were allowed to recover in RA until P21 with no further treatment. Whole brains were harvested for histopathology and morphometric analyses, and assessed for biomarkers of oxidative stress and inflammation, as well as myelin injury. Neonatal IH resulted in higher brain/body weight ratios, an effect that was reversed with n-3 PUFAs and n-3 PUFAs+CoQ10 with or without ketorolac. Neonatal IH was also associated with hemorrhage, oxidative stress, and elevations in inflammatory prostanoids. Supplementation with n-3 PUFAs and nGSH with and without ketorolac were most beneficial for myelin growth and integrity when administered in RA. However, the benefit of n-3 PUFAs was significantly curtailed in neonatal IH. Neonatal IH during a critical time of brain development causes inflammation and oxidative injury. Loss of therapeutic benefits of n-3 PUFAs suggest its susceptibility to oxidation in neonatal IH and therefore indicate that co-administration with antioxidants may be necessary to sustain its efficacy.