The Relationship Between Diet, Gut Microbiota, and Serum Metabolome of South Asian Infants at 1 Year.

BACKGROUND: Diet is known to affect the gut microbiota and the serum metabolome in adults, but this has not been fully explored in infants. Infancy is an important developmental period that may influence a person's long-term health. Infant development can be affected by diet, which also interacts with the developing gut microbiota. OBJECTIVES: This study aimed to explore the associations between diet, the gut microbiota, and the serum metabolome of 1-y-old infants with the overarching goal of identifying serum biomarkers of diet and/or the gut microbiota. METHODS: We derived dietary patterns of 1-y-old infants (n = 182) participating in the Canadian South Asian Birth Cohort (START) study. We compared gut microbiota α-diversity and ß-diversity and taxa relative abundance from 16S rRNA gene profiles with dietary patterns (PERMANOVA, Envfit) and investigated diet-serum metabolite associations using a multivariate analysis (partial least squares-discriminant analysis) and univariate analysis (t test). We explored the effect of nondietary factors on diet-serum metabolite relationships by incorporating diet, the gut microbiota, and maternal, perinatal, and infant characteristics in a multivariable forward stepwise regression. We replicated this analysis in White European infants, from the CHILD Cohort Study (n = 81). RESULTS: A dietary pattern characterized by formula consumption and negatively associated with breastfeeding most strongly predicted variation in the gut microbiota (R2 = 0.109) and serum metabolome (R2 = 0.547). Breastfed participants showed higher abundance of microbes from the genera Bifidobacterium (3.29 log2-fold) and Lactobacillus (7.93 log2-fold) and higher median concentrations of the metabolites S-methylcysteine (1.38 µM) and tryptophan betaine (0.43 µM) than nonbreastfed participants. Formula consuming infants showed higher median concentrations of branched-chain/aromatic amino acids (average 48.3 µM) than non-formula-consuming infants. CONCLUSIONS: Formula consumption and breastfeeding most strongly predicted the serum metabolites of 1-y-old infants, even when the gut microbiota, solid food consumption, and other covariates were considered.

Pregnancy outcomes in women taking probiotics or prebiotics: a systematic review and meta-analysis.

BACKGROUND: Probiotics are living microorganisms that, when administered in adequate amounts, confer a health benefit. It has been speculated that probiotics might help prevent preterm birth, but in two previous systematic reviews possible major increases in this risk have been suggested. Our objective was to perform a systematic review and meta-analysis of the risk of preterm birth and other adverse pregnancy outcomes in pregnant women taking probiotics, prebiotics or synbiotics. METHODS: We searched six electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science's Core collection and BIOSIS Preview) up to September 2016 and contacted authors for additional data. We included randomized controlled trials in which women with a singleton pregnancy received a probiotic, prebiotic or synbiotic intervention. Two independent reviewers extracted data using a piloted form and assessed the risk of bias using the Cochrane risk of bias tool. We used random-effects meta-analyses to pool the results. RESULTS: We identified 2574 publications, screened 1449 non-duplicate titles and abstracts and read 160 full text articles. The 49 publications that met our inclusion criteria represented 27 studies. No study used synbiotics, one used prebiotics and the rest used probiotics. Being randomized to take probiotics during pregnancy neither increased nor decreased the risk of preterm birth < 34 weeks (RR 1.03, 95% CI 0.29-3.64, I2 0%, 1017 women in 5 studies), preterm birth < 37 weeks (RR 1.08, 95% CI 0.71-1.63, I2 0%, 2484 women in 11 studies), or most of our secondary outcomes, including gestational diabetes mellitus. CONCLUSIONS: We found no evidence that taking probiotics or prebiotics during pregnancy either increases or decreases the risk of preterm birth or other infant and maternal adverse pregnancy outcomes. TRIAL REGISTRATION: We prospectively published the protocol for this study in the PROSPERO database ( CRD42016048129 ).

A comparison of intestinal microbiota in a population of low-risk infants exposed and not exposed to intrapartum antibiotics: The Baby & Microbiota of the Intestine cohort study protocol.

BACKGROUND: The intestinal microbiota influences metabolic, nutritional, and immunologic processes and has been associated with a broad range of adverse health outcomes including asthma, obesity and Type 2 diabetes. Early life exposures may alter the course of gut microbial colonization leading to differences in metabolic and immune regulation throughout life. Although approximately 50 % of low-risk full-term infants born in Canada are exposed to intrapartum antibiotics, little is known about the influence of this common prophylactic treatment on the developing neonatal intestinal microbiota. The purpose of this study is to describe the intestinal microbiome over the first 3 years of life among healthy, breastfed infants born to women with low-risk pregnancies at full term gestation and to determine if at 1 year of age, the intestinal microbiome of infants exposed to intrapartum antibiotics differs in type and quantity from the infants that are not exposed. METHODS: A prospectively followed cohort of 240 mother-infant pairs will be formed by enrolling eligible pregnant women from midwifery practices in the City of Hamilton and surrounding area in Ontario, Canada. Participants will be followed until the age of 3 years. Women are eligible to participate in the study if they are considered to be low-risk, planning a vaginal birth and able to communicate in English. Women are excluded if they have a multiple pregnancy or a preterm birth. Study questionnaires are completed, anthropometric measures are taken and biological samples are acquired including eight infant stool samples between 3 days and 3 years of age. DISCUSSION: Our experience to date indicates that midwifery practices and clients are keen to participate in this research. The midwifery client population is likely to have high rates of breastfeeding and low rates of intervention, allowing us to examine the comparative development of the microbiome in a relatively healthy and homogenous population. Results from this study will make an important contribution to the growing understanding of the patterns of intestinal microbiome colonization in the early years of life and may have implications for best practices to support the establishment of the microbiome at birth.

Integrative multiomics analysis of infant gut microbiome and serum metabolome reveals key molecular biomarkers of early onset childhood obesity.

Evidence supports a complex interplay of gut microbiome and host metabolism as regulators of obesity. The metabolic phenotype and microbial metabolism of host diet may also contribute to greater obesity risk in children early in life. This study aimed to identify features that discriminated overweight/obese from normal weight infants by integrating gut microbiome and serum metabolome profiles. This prospective analysis included 50 South Asian children living in Canada, selected from the SouTh Asian biRth cohorT (START). Serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry and the relative abundance of bacterial 16S rRNA gene amplicon sequence variant was evaluated at 1 year. Cumulative body mass index (BMIAUC) and skinfold thickness (SSFAUC) scores were calculated from birth to 3 years as the total area under the growth curve (AUC). BMIAUC and/or SSFAUC >85th percentile was used to define overweight/obesity. Data Integration Analysis for Biomarker discovery using Latent cOmponent (DIABLO) was used to identify discriminant features associated with childhood overweight/obesity. The associations between identified features and anthropometric measures were examined using logistic regression. Circulating metabolites including glutamic acid, acetylcarnitine, carnitine, and threonine were positively, whereas γ-aminobutyric acid (GABA), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were negatively associated with childhood overweight/obesity. The abundance of the Pseudobutyrivibrio and Lactobacillus genera were positively, and Clostridium sensu stricto 1 and Akkermansia were negatively associated with childhood overweight/obesity. Integrative analysis revealed that Akkermansia was positively whereas Lactobacillus was inversely correlated with GABA and SDMA, and Pseudobutyrivibrio was inversely correlated with GABA. This study provides insights into metabolic and microbial signatures which may regulate satiety, energy metabolism, inflammatory processes, and/or gut barrier function, and therefore, obesity trajectories in childhood. Understanding the functional capacity of these molecular features and potentially modifiable risk factors such as dietary exposures early in life may offer a novel approach for preventing childhood obesity.

A culturally tailored personaliseD nutrition intErvention in South ASIan women at risk of Gestational Diabetes Mellitus (DESI-GDM): a randomised controlled trial protocol.

INTRODUCTION: South Asians are more likely to develop gestational diabetes mellitus (GDM) than white Europeans. Diet and lifestyle modifications may prevent GDM and reduce undesirable outcomes in both the mother and offspring. Our study seeks to evaluate the effectiveness and participant acceptability of a culturally tailored, personalised nutrition intervention on the glucose area under the curve (AUC) after a 2-hour 75 g oral glucose tolerance test (OGTT) in pregnant women of South Asian ancestry with GDM risk factors. METHODS AND ANALYSIS: A total of 190 South Asian pregnant women with at least 2 of the following GDM risk factors-prepregnancy body mass index>23, age>29, poor-quality diet, family history of type 2 diabetes in a first-degree relative or GDM in a previous pregnancy will be enrolled during gestational weeks 12-18, and randomly assigned in a 1:1 ratio to: (1) usual care, plus weekly text messages to encourage walking and paper handouts or (2) a personalised nutrition plan developed and delivered by a culturally congruent dietitian and health coach; and FitBit to track steps. The intervention lasts 6-16 weeks, depending on week of recruitment. The primary outcome is the glucose AUC from a three-sample 75 g OGTT 24-28 weeks' gestation. The secondary outcome is GDM diagnosis, based on Born-in-Bradford criteria (fasting glucose>5.2 mmol/L or 2 hours post load>7.2 mmol/L). ETHICS AND DISSEMINATION: The study has been approved by the Hamilton Integrated Research Ethics Board (HiREB #10942). Findings will be disseminated among academics and policy-makers through scientific publications along with community-orientated strategies. TRIAL REGISTRATION NUMBER: NCT03607799.

Effects of bacterial ACC deaminase on Brassica napus gene expression.

Plants in association with plant growth-promoting rhizobacteria can benefit from lower plant ethylene levels through the action of the bacterial enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. This enzyme cleaves the immediate biosynthetic precursor of ethylene, ACC. Ethylene is responsible for many aspects of plant growth and development but, under stressful conditions, it exacerbates stress symptoms. The ACC deaminase-containing bacterium Pseudomonas putida UW4 is a potent plant growth-promoting strain and, as such, was used to elaborate the detailed role of bacterial ACC deaminase in Brassica napus (canola) plant growth promotion. Transcriptional changes in bacterially treated canola plants were investigated with the use of an Arabidopsis thaliana oligonucleotide microarray. A heterologous approach was necessary because there are few tools available at present to measure global expression changes in nonmodel organisms, specifically with the sensitivity of microarrays. The results indicate that the transcription of genes involved in plant hormone regulation, secondary metabolism, and stress response was altered in plants by the presence of the bacterium, whereas the upregulation of genes for auxin response factors and the downregulation of stress response genes was observed only in the presence of bacterial ACC deaminase. These results support the suggestion that there is a direct link between ethylene and the auxin response, which has been suggested from physiological studies, and provide more evidence for the stress-reducing benefits of ACC deaminase-expressing plant growth-promoting bacteria.

Sources of Variation in Food-Related Metabolites during Pregnancy.

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.

Capturing the antibiotic resistome of preterm infants reveals new benefits of probiotic supplementation.

BACKGROUND: Probiotic use in preterm infants can mitigate the impact of antibiotic exposure and reduce rates of certain illnesses; however, the benefit on the gut resistome, the collection of antibiotic resistance genes, requires further investigation. We hypothesized that probiotic supplementation of early preterm infants (born < 32-week gestation) while in hospital reduces the prevalence of antibiotic resistance genes associated with pathogenic bacteria in the gut. We used a targeted capture approach to compare the resistome from stool samples collected at the term corrected age of 40 weeks for two groups of preterm infants (those that routinely received a multi-strain probiotic during hospitalization and those that did not) with samples from full-term infants at 10 days of age to identify if preterm birth or probiotic supplementation impacted the resistome. We also compared the two groups of preterm infants up to 5 months of age to identify persistent antibiotic resistance genes. RESULTS: At the term corrected age, or 10 days of age for the full-term infants, we found over 80 antibiotic resistance genes in the preterm infants that did not receive probiotics that were not identified in either the full-term or probiotic-supplemented preterm infants. More genes associated with antibiotic inactivation mechanisms were identified in preterm infants unexposed to probiotics at this collection time-point compared to the other infants. We further linked these genes to mobile genetic elements and Enterobacteriaceae, which were also abundant in their gut microbiomes. Various genes associated with aminoglycoside and beta-lactam resistance, commonly found in pathogenic bacteria, were retained for up to 5 months in the preterm infants that did not receive probiotics. CONCLUSIONS: This pilot survey of preterm infants shows that probiotics administered after preterm birth during hospitalization reduced the diversity and prevented persistence of antibiotic resistance genes in the gut microbiome. The benefits of probiotic use on the microbiome and the resistome should be further explored in larger groups of infants. Due to its high sensitivity and lower sequencing cost, our targeted capture approach can facilitate these surveys to further address the implications of resistance genes persisting into infancy without the need for large-scale metagenomic sequencing. Video Abstract.

Generation of multimillion-sequence 16S rRNA gene libraries from complex microbial communities by assembling paired-end illumina reads.

Microbial communities host unparalleled taxonomic diversity. Adequate characterization of environmental and host-associated samples remains a challenge for microbiologists, despite the advent of 16S rRNA gene sequencing. In order to increase the depth of sampling for diverse bacterial communities, we developed a method for sequencing and assembling millions of paired-end reads from the 16S rRNA gene (spanning the V3 region; ∼200 nucleotides) by using an Illumina genome analyzer. To confirm reproducibility and to identify a suitable computational pipeline for data analysis, sequence libraries were prepared in duplicate for both a defined mixture of DNAs from known cultured bacterial isolates (>1 million postassembly sequences) and an Arctic tundra soil sample (>6 million postassembly sequences). The Illumina 16S rRNA gene libraries represent a substantial increase in number of sequences over all extant next-generation sequencing approaches (e.g., 454 pyrosequencing), while the assembly of paired-end 125-base reads offers a methodological advantage by incorporating an initial quality control step for each 16S rRNA gene sequence. This method incorporates indexed primers to enable the characterization of multiple microbial communities in a single flow cell lane, may be modified readily to target other variable regions or genes, and demonstrates unprecedented and economical access to DNAs from organisms that exist at low relative abundances.

Investigating colonization patterns of the infant gut microbiome during the introduction of solid food and weaning from breastmilk: A cohort study protocol.

The first exposures to microbes occur during infancy and it is suggested that this initial colonization influences the adult microbiota composition. Despite the important role that the gut microbiome may have in health outcomes later in life, the factors that influence its development during infancy and early childhood have not been characterized fully. Guidelines about the introduction of solid foods and cessation of breastfeeding, which is thought to have a significant role in the transition to a more adult-like microbiota, are not based on microbiome research. There is even less understanding of approaches used to transition to solid food in the preterm population. The purpose of this study is to identify the impact of early life dietary events on gut microbiome community structures and function among infants born at term and pre-term. We plan to prospectively monitor the gut microbiome of infants during two critical timepoints in microbial development: the introduction of solid foods and cessation from breastmilk. A total of 35 participants from three primary observational birth cohorts (two full-term cohorts and one pre-term cohort) will be enrolled in this sub-study. Participants will be asked to collect stool samples and fill out a study diary before, during and after the introduction of solids and again during weaning from breastmilk. We will use frequent fecal sampling analyzed using 16S rRNA gene profiling, metagenomics, metabolomics, and targeted bacterial culturing to identify and characterize the microbial communities, as well as provide insight into the phenotypic characteristics and functional capabilities of the microbes present during these transitional periods of infancy. This study will provide a comprehensive approach to detailing the effects of dietary transition from breastmilk to a more adult-like solid food diet on the microbiome and in doing so will contribute to evidence-based infant nutrition guidance.

Association of gut microbiome with fasting triglycerides, fasting insulin and obesity status in Mexican children.

BACKGROUND: The association of gut microbiota with obesity and its cardio-metabolic complications in paediatric populations is still controversial. OBJECTIVE: We investigated the association of obesity and cardio-metabolic traits with gut microbiota on 167 and 163 children with normal weight and obesity from Mexico City and Oaxaca, Mexico. METHODS: Anthropometric and biochemical traits were measured. The microbial communities were determined by high-throughput sequencing of bacterial 16S rRNA gene v3-v4 region. RESULTS: The gut microbial community structure was associated with obesity and fasting plasma insulin (FPI) in Mexico City (PObesity = 0.012, PFPI = 0.0003) and Oaxaca (PObesity = 0.034, PFPI = 0.016), and with triglycerides (TG) in Oaxaca (P = .0002). The Firmicutes/Bacteroidetes ratio was positively associated with TG in Oaxaca (P = .003). Firmicutes and Bacteroidetes phyla were positively and negatively associated with obesity (Mexico City: PFirmicutes = 0.013, PBacteroidetes = 0.009) and TG (Oaxaca: PFirmicutes = 0.002, PBacteroidetes = 0.004). In Oaxaca, Verrucomicrobia was negatively associated with obesity (P = .004). In Mexico City, the bacterial genus Fusicatenibacter, Romboutsia, Ruminococcaceae, Ruminiclostridium, Blautia, Clostridium, Anaerostipes and Intestinibacter were associated with obesity and FPI, while in Oaxaca, Bacteroides, Alistipes and Clostridium were associated with TG. CONCLUSION: The gut microbial community structure in children is associated with obesity and FPI in Mexico City, and with obesity, FPI and TG in Oaxaca.

Infants' First Solid Foods: Impact on Gut Microbiota Development in Two Intercontinental Cohorts.

The introduction of solid foods is an important dietary event during infancy that causes profound shifts in the gut microbial composition towards a more adult-like state. Infant gut bacterial dynamics, especially in relation to nutritional intake remain understudied. Over 2 weeks surrounding the time of solid food introduction, the day-to-day dynamics in the gut microbiomes of 24 healthy, full-term infants from the Baby, Food & Mi and LucKi-Gut cohort studies were investigated in relation to their dietary intake. Microbial richness (observed species) and diversity (Shannon index) increased over time and were positively associated with dietary diversity. Microbial community structure (Bray-Curtis dissimilarity) was determined predominantly by individual and age (days). The extent of change in community structure in the introductory period was negatively associated with daily dietary diversity. High daily dietary diversity stabilized the gut microbiome. Bifidobacterial taxa were positively associated, while taxa of the genus Veillonella, that may be the same species, were negatively associated with dietary diversity in both cohorts. This study furthers our understanding of the impact of solid food introduction on gut microbiome development in early life. Dietary diversity seems to have the greatest impact on the gut microbiome as solids are introduced.

Persistence of Suspected Probiotic Organisms in Preterm Infant Gut Microbiota Weeks After Probiotic Supplementation in the NICU.

Probiotics are becoming a prevalent supplement to prevent necrotizing enterocolitis in infants born preterm. However, little is known about the ability of these live bacterial supplements to colonize the gut or how they affect endogenous bacterial strains and the overall gut community. We capitalized on a natural experiment resulting from a policy change that introduced the use of probiotics to preterm infants in a single Neonatal Intensive Care Unit. We used amplicon sequence variants (ASVs) derived from the v3 region of the 16S rRNA gene to compare the prevalence and abundance of Bifidobacterium and Lactobacillus in the gut of preterm infants who were and were not exposed to a probiotic supplement in-hospital. Infants were followed to 5 months corrected age. In the probiotic-exposed infants, ASVs belonging to species of Bifidobacterium appeared at high relative abundance during probiotic supplementation and persisted for up to 5 months. In regression models that controlled for the confounding effects of age and antibiotic exposure, probiotic-exposed infants had a higher abundance of the suspected probiotic bifidobacteria than unexposed infants. Conversely, the relative abundance of Lactobacillus was similar between preterm groups over time. Lactobacillus abundance was inversely related to antibiotic exposure. Furthermore, the overall gut microbial community of the probiotic-exposed preterm infants at term corrected age clustered more closely to samples collected from 10-day old full-term infants than to samples from unexposed preterm infants at term age. In conclusion, routine in-hospital administration of probiotics to preterm infants resulted in the potential for colonization of the gut with probiotic organisms post-discharge and effects on the gut microbiome as a whole. Further research is needed to fully discriminate probiotic bacterial strains from endogenous strains and to explore their functional role in the gut microbiome and in infant health.

Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice.

The hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA-mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.This article has an associated First Person interview with the first author of the paper.

Culture and Molecular Profiling of the Respiratory Tract Microbiota.

Microbiome research of host-associated communities has been advanced recently through improvements in sequencing technologies and bioinformatic methods. Traditional microbiological culture, when combined with molecular techniques, can provide a sensitive platform to comprehensively study the airway microbiota. Here we describe the culture methods necessary to capture a large proportion of the airway microbiota and molecular methods for profiling bacterial communities through the 16S rRNA gene, which, when combined, offer a more complete picture of the diversity of airway microbial communities than either method alone.

Long term but not short term exposure to obesity related microbiota promotes host insulin resistance.

The intestinal microbiota and insulin sensitivity are rapidly altered after ingestion of obesogenic diets. We find that changes in the composition of the fecal microbiota precede changes in glucose tolerance when mice are fed obesogenic, low fiber, high fat diets (HFDs). Antibiotics alter glycemia during the first week of certain HFDs, but antibiotics show a more robust improvement in glycemic control in mice with protracted obesity caused by long-term feeding of multiple HFDs. Microbiota transmissible dysglycemia and glucose intolerance only occur when germ-free mice are exposed to obesity-related microbes for more than 45 days. We find that sufficient host exposure time to microbiota derived from HFD-fed mice allows microbial factors to contribute to insulin resistance, independently from increased adiposity in mice. Our results are consistent with intestinal microbiota contributing to chronic insulin resistance and dysglycemia during prolonged obesity, despite rapid diet-induced changes in the taxonomic composition of the fecal microbiota.

Intrapartum antibiotics for GBS prophylaxis alter colonization patterns in the early infant gut microbiome of low risk infants.

Early life microbial colonization and succession is critically important to healthy development with impacts on metabolic and immunologic processes throughout life. A longitudinal prospective cohort was recruited from midwifery practices to include infants born at full term gestation to women with uncomplicated pregnancies. Here we compare bacterial community succession in infants born vaginally, with no exposure to antibiotics (n = 53), with infants who were exposed to intrapartum antibiotic prophylaxis (IAP) for Group B Streptococcus (GBS; n = 14), and infants born by C-section (n = 7). Molecular profiles  of the 16 S rRNA genes indicate that there is a delay in the expansion of Bifidobacterium, which was the dominate infant gut colonizer, over the first 12 weeks and a persistence of Escherichia when IAP for GBS exposure is present during vaginal labour. Longer duration of IAP exposure increased the magnitude of the effect on Bifidobacterium populations, suggesting a longer delay in microbial community maturation. As with prior studies, we found altered gut colonisation following C-section that included a notable lack of Bacteroidetes. This study found that exposure of infants to IAP for GBS during vaginal birth affected aspects of gut microbial ecology that, although dramatic at early time points, disappeared by 12 weeks of age in most infants.

Association of high-risk sexual behaviour with diversity of the vaginal microbiota and abundance of Lactobacillus.

OBJECTIVE: To compare the vaginal microbiota of women engaged in high-risk sexual behaviour (sex work) with women who are not engaged in high-risk sexual behaviour. Diverse vaginal microbiota, low in Lactobacillus species, like those in bacterial vaginosis (BV), are associated with increased prevalence of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) acquisition. Although high-risk sexual behaviour increases risk for STIs, the vaginal microbiota of sex workers is understudied. METHODS: A retrospective cross-sectional study was conducted comparing vaginal microbiota of women who are not engaged in sex work (non-sex worker controls, NSW, N = 19) and women engaged in sex work (female sex workers, FSW, N = 48), using Illumina sequencing (16S rRNA, V3 region). RESULTS: Bacterial richness and diversity were significantly less in controls, than FSW. Controls were more likely to have Lactobacillus as the most abundant genus (58% vs. 17%; P = 0.002) and composition of their vaginal microbiota differed from FSW (PERMANOVA, P = 0.001). Six microbiota clusters were detected, including a high diversity cluster with three sub-clusters, and 55% of women with low Nugent Scores fell within this cluster. High diversity was observed by 16S sequencing in FSW, regardless of Nugent Scores, suggesting that Nugent Score may not be capable of capturing the diversity present in the FSW vaginal microbiota. CONCLUSIONS: High-risk sexual behaviour is associated with diversity of the vaginal microbiota and lack of Lactobacillus. These factors could contribute to increased risk of STIs and HIV in women engaged in high-risk sexual behaviour.

Muramyl Dipeptide-Based Postbiotics Mitigate Obesity-Induced Insulin Resistance via IRF4.

Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome. MDP reduced hepatic insulin resistance during obesity and low-level endotoxemia. NOD1-activating muropeptides worsened glucose tolerance. IRF4 distinguished opposing glycemic responses to different types of peptidoglycan and was required for MDP/NOD2-induced insulin sensitization and lower metabolic tissue inflammation during obesity and endotoxemia. IRF4 was dispensable for exacerbated glucose intolerance via NOD1. Mifamurtide, an MDP-based drug with orphan drug status, was an insulin sensitizer at clinically relevant doses in obese mice.

Ethnic and diet-related differences in the healthy infant microbiome.

BACKGROUND: The infant gut is rapidly colonized by microorganisms soon after birth, and the composition of the microbiota is dynamic in the first year of life. Although a stable microbiome may not be established until 1 to 3 years after birth, the infant gut microbiota appears to be an important predictor of health outcomes in later life. METHODS: We obtained stool at one year of age from 173 white Caucasian and 182 South Asian infants from two Canadian birth cohorts to gain insight into how maternal and early infancy exposures influence the development of the gut microbiota. We investigated whether the infant gut microbiota differed by ethnicity (referring to groups of people who have certain racial, cultural, religious, or other traits in common) and by breastfeeding status, while accounting for variations in maternal and infant exposures (such as maternal antibiotic use, gestational diabetes, vegetarianism, infant milk diet, time of introduction of solid food, infant birth weight, and weight gain in the first year). RESULTS: We demonstrate that ethnicity and infant feeding practices independently influence the infant gut microbiome at 1 year, and that ethnic differences can be mapped to alpha diversity as well as a higher abundance of lactic acid bacteria in South Asians and a higher abundance of genera within the order Clostridiales in white Caucasians. CONCLUSIONS: The infant gut microbiome is influenced by ethnicity and breastfeeding in the first year of life. Ethnic differences in the gut microbiome may reflect maternal/infant dietary differences and whether these differences are associated with future cardiometabolic outcomes can only be determined after prospective follow-up.