Microbial Changes during Pregnancy, Birth, and Infancy

Several healthy developmental processes such as pregnancy, fetal development and infant development include a multitude of physiological changes: weight gain, hormonal and metabolic changes, as well as immune changes. In this review we present an additional important factor which both influences and is affected by these physiological processes- the microbiome. We summarize the known changes in microbiota composition at a variety of body sites including gut, vagina, oral cavity and placenta, throughout pregnancy, fetal development and early childhood. There is still a lot to be discovered; yet several pieces of research point to the healthy desired microbial changes. Future research is likely to unravel precise roles and mechanisms of the microbiota in gestation; perhaps linking the metabolic, hormonal and immune changes together. Although some research has started to link microbial dysbiosis and specific microbial populations with unhealthy pregnancy complications, it is important to first understand the context of the natural healthy microbial changes occurring. Until recently the placenta and developing fetus were considered to be germ free, containing no apparent microbiome. We present multiple study results showing distinct microbiota compositions in the placenta and meconium, alluding to early microbial colonization. These results may change dogmas and our overall understanding of the importance and roles of microbiota from the beginning of life. We further review the main factors shaping the infant microbiome- modes of delivery, feeding, weaning, and exposure to antibiotics. Taken together, we are starting to build a broader understanding of healthy vs. abnormal microbial alterations throughout major developmental time-points

Intraoperative pain during caesarean delivery: Incidence, risk factors and physician perception

Background: Intraoperative pain is a possible complication of neuraxial anaesthesia for caesarean delivery. There is little information available about its incidence, risk factors and physician perception. Methods: Parturients undergoing spinal anaesthesia for elective caesarean delivery were enrolled. Before surgery, parturients were asked about preoperative anxiety on a verbal numerical scale (VNS), anticipated analgesic requirement, postoperative pain levels, Spielberger STATE-TRAIT inventory index, Pain Catastrophizing Scale. After surgery, parturients were asked to answer questions (intraoperative VNS pain). The anaesthesiologist and obstetrician were asked to fill out a questionnaire asking about perceived intraoperative pain. Influence of preoperative anxiety on intraoperative pain (yes/no) was assessed using logistic regression. Mc Fadden's R2 was calculated. The agreement in physician perception of intraoperative pain with reported pain by the parturient was examined by calculating Cohen's kappa and 95% Confidence Intervals (CI). Results: We included 193 parturients in our analysis. Incidence of intraoperative pain was 11.9%. Median intraoperative VNS pain of parturients with pain was 4.0 (1st quartile 4.0; 3rd quartile 9.0). Preoperative anxiety was not a good predictor of intraoperative pain (p-value of β-coefficient = 0.43, Mc Fadden's R2 = 0.01). Including further preoperative variables did not result in a good prediction model. Cohen's kappa between reported pain by parturient and by the obstetrician was 0.21 (95% CI: 0.01, 0.41) and by the anaesthesiologist was 0.3 (95% CI: 0.12, 0.48). Conclusions: We found a substantial incidence (11.9%) of intraoperative pain during caesarean delivery. Preoperative anxiety did not predict intraoperative pain. Physicians did not accurately identify parturients' intraoperative pain. Significance: Intraoperative pain occurred in 11.9% and severe intraoperative pain occurred in 1.11% of parturients undergoing elective caesarean delivery under spinal anaesthesia. We did not find any preoperative variables that could reliably predict intraoperative pain. Obstetricians and anaesthesiologists underestimated the incidence of intraoperative pain in our cohort and thus, more attention must be put to parturients' pain

Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index. In this study, Omry Koren, Samuli Rautava and colleagues report a sex-specific association between neonatal antibiotic exposure and weight and height gain during the first six years of life and showing that boys but not girls exposed to neonatal antibiotics exhibit impaired weight and height development

Characterizing the gut (Gallus gallus) microbiota following the consumption of an iron biofortified Rwandan cream seeded carioca (Phaseolus Vulgaris L.) bean-based diet

Biofortification is a plant breeding method that introduces increased concentrations of minerals in staple food crops (e.g., legumes, cereal grains), and has shown success in alleviating insufficient Fe intake in various human populations. Unlike other strategies utilized to alleviate Fe deficiency, studies of the gut microbiota in the context of Fe biofortification have not yet been reported, although the consumption of Fe biofortified staple food crops has increased significantly over time. Hence, in this study, we performed a 6-week feeding trial in Gallus gallus (n = 14), aimed to investigate the alterations in the gut microbiome following administration of an Fe biofortified bean-based diet (biofortified, BFe) versus a bean based diet with poorly-bioavailable Fe (standard, SFe). Cream seeded carioca bean based diets were designed in an identical fashion to those used in a recent human clinical trial of Fe biofortified beans in Rwanda. We hypothesized that the different dietary Fe contents in the beans based diets will alter the composition and function of the intestinal microbiome. The primary outcomes were changes in the gut microbiome composition and function analyzed by 16S rRNA gene sequencing. We observed no significant changes in phylogenetic diversity between groups. There were significant differences in the composition of the microbiota between groups, with the BFe group harboring fewer taxa participating in bacterial Fe uptake, increased abundance of bacteria involved in phenolic catabolism, and increased abundance of beneficial butyrate-producing bacteria. Additionally, depletion of key bacterial pathways responsible for bacterial viability and Fe uptake suggest that improvements in Fe bioavailability, in addition to increases in Fe-polyphenol and Fe-phytate complexes due to biofortification, led to decreased concentrations of cecal Fe available for bacterial utilization. Our findings demonstrate that Fe biofortification may improve Fe status without negatively altering the structure and function of the gut microbiota, as is observed with other nutritional methods of Fe supplementation. These results may be used to further improve the efficacy and safety of future biofortification efforts in eradicating global Fe deficiency.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Chronic Zinc Deficiency Alters Chick Gut Microbiota Composition and Function

Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host under conditions of Zn deficiency have yet to be studied. Using the broiler chicken (Gallus gallus) model, the aim of this study was to characterize distinct cecal microbiota shifts induced by chronic dietary Zn depletion. We demonstrate that Zn deficiency induces significant taxonomic alterations and decreases overall species richness and diversity, establishing a microbial profile resembling that of various other pathological states. Through metagenomic analysis, we show that predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways responsible for macro- and micronutrient uptake are significantly depleted under Zn deficiency; along with concomitant decreases in beneficial short chain fatty acids, such depletions may further preclude optimal host Zn availability. We also identify several candidate microbes that may play a significant role in modulating the bioavailability and utilization of dietary Zn during prolonged deficiency. Our results are the first to characterize a unique and dysbiotic cecal microbiota during Zn deficiency, and provide evidence for such microbial perturbations as potential effectors of the Zn deficient phenotype

New Insights on the Nutrition Status and Antioxidant Capacity in Multiple Sclerosis Patients

Background: Multiple sclerosis (MS) is a multifactorial disease with unknown etiology. It is assumed to result from interplay between genetic and environmental factors, including nutrition. We hypothesized that there are differences in nutritional parameters between MS patients and healthy controls. Methods: We examined 63 MS patients and 83 healthy controls. Nutritional status was determined by a dietary questionnaire, blood tests, quantification of cell membrane fatty acids, and serum antioxidant capacity. Results: We found that MS patients consumed a more limited diet compared with the healthy group, indicated by a lower average of 31 nutrients and by consumption levels of zinc and thiamine below the recommended daily intake. Both consumption and measured iron values were significantly lower in MS patients, with the lowest measures in the severe MS group. Long saturated fatty acids (>C16) were significantly lower in MS patients, while palmitic and palmitoleic acids were both higher. Serum total antioxidant capacity was significantly lower in the MS group compared with healthy controls, with the lowest measures in patients with severe MS. Conclusions: This study points to a possible correlation between nutritional status and MS. Understanding the clinical meaning of these findings will potentially allow for the development of future personalized dietary interventions as part of MS treatment

Tuftsin-Phosphorylcholine Maintains Normal Gut Microbiota in Collagen Induced Arthritic Mice

Rheumatoid arthritis (RA) is characterized by chronic autoinflammation of the joints, with a prevalence of about 1% in Western populations. Evidence in recent years has linked RA to changes in the gut microbiota (dysbiosis). Interestingly, helminths have been shown to have therapeutic activity in RA. Specifically, a glycoprotein containing phosphorylcholine (PC) extracted from helminths was found to have immunomodulatory activity. We have previously developed a novel chimeric compound composed of tuftsin-PC (TPC) that attenuates the joint destruction in mice with collagen-induced arthritis (CIA). Here, we address the interrelationship between TPC immunomodulatory activity and the gut microbiota in CIA mice. Preventive therapy with TPC in mice with arthritis maintained a physiological arthritis score as well as a steady gut microbial environment, similar to that of healthy controls, in contrast to CIA mice with severe disease. The microbial composition differed significantly between healthy and phosphate-buffered saline-treated CIA mice, enabling classifying test samples by machine learning based on levels of a small number of bacterial species. Using these bacterial biomarkers, all TPC-treated CIA mice were classified as healthy. Thus, we describe a clear correlation between TPC treatment, healthy gut microbial communities, and prevention of arthritis. This is the first study to demonstrate the immunomodulatory effect of helminth derivatives in autoimmune diseases and the link to gut microbiota

Family and genus level cecal microbiota shifts between the BFe and SFe treatment groups.

<p>(a) Family level changes in the BFe and SFe groups as measured at the end of the study (day 42); (b) Genus level changes in the BFe and SFe groups as measured at the end of the study (day 42).</p

LEfSe method identifying the OTUs with the greatest differences in abundance in the BFe and SFe groups.

<p>(a) Taxonomic cladogram obtained using LEfSe analysis of the 16S rRNA sequences. Treatment groups are indicated by the different colors; (b) Computed LDA scores of the relative abundance difference between the BFe and SFe groups. Comparison of the relative abundance at the (c) phylum; (d) order; (e) family; and (f) genus levels in the BFe and SFe groups.</p