Maternal psychological distress before birth influences gut immunity in mid-infancy.

BACKGROUND: Maternal pre-postnatal psychosocial distress increases the risk for childhood allergic disease. This may occur through a host immunity pathway that involves intestinal secretory immunoglobulin A (sIgA). Experimental animal models show changes in the gut microbiome and immunity of offspring when exposed to direct or prenatal maternal stress, but little is known in humans. OBJECTIVE: We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. METHODS: 1043 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort were studied. Trajectories of maternal perceived stress and depression were based on scored scales administered in pregnancy and postpartum. sIgA was quantified in infant stool (mean age 3.7 months) with Immundiagnostik ELISA. Linear regression and logistic regression were employed to test associations. RESULTS: Very low fecal sIgA concentrations were more common in infants of mothers in the antepartum and persistent depression trajectories (6% and 2% of women, respectively). Independent of breastfeeding status at fecal sampling, infant antibiotic exposure or other covariates, the antepartum depressive symptom trajectory was associated with reduced mean infant sIgA concentrations (ß=-0.07, P < .01) and a two fold risk for lowest quartile concentrations (OR, 1.86; 95% CI: 1.02, 3.40). This lowering of sIgA yielded a large effect size in older infants (4-8 months)-breastfed and not. No associations were seen with postpartum depressive symptoms (7% of women) or with any of the perceived stress trajectories. CONCLUSION AND CLINICAL RELEVANCE: Despite improved mood postpartum and independent of breastfeeding status, mothers experiencing antepartum depressive symptoms delivered offspring who exhibited lower fecal sIgA concentrations especially in later infancy. The implications of lowered sIgA concentrations in infant stool are altered microbe-sIgA interactions, greater risk for C difficile colonization and atopic disease in later years.

Maternal depressive symptoms linked to reduced fecal Immunoglobulin A concentrations in infants.

Secretory Immunoglobulin A (sIgA) plays a critical role to infant gut mucosal immunity. Delayed IgA production is associated with greater risk of allergic disease. Murine models of stressful events during pregnancy and infancy show alterations in gut immunity and microbial composition in offspring, but little is known about the stress-microbiome-immunity pathways in humans. We investigated differences in infant fecal sIgA concentrations according to the presence of maternal depressive symptoms during and after pregnancy. A subsample of 403 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort were studied. Their mothers completed the Center of Epidemiologic Studies Depression Scale when enrolled prenatally and again postpartum. Quantified by Immundiagnostik sIgA ELISA kit, sIgA from infant stool was compared across maternal depressive symptom categories using Mann-Whitney U-tests and logistic regression models that controlled for various covariates. Twelve percent of women reported clinically significant depressive symptoms only prenatally, 8.7% had only postpartum symptoms and 9.2% had symptoms both pre and postnatally. Infants born to mothers with pre and postnatal symptoms had significantly lower median sIgA concentrations than those in the reference group (4.4 mg/g feces vs. 6.3 mg/g feces; p = 0.033). The odds for sIgA concentrations in the lowest quartile was threefold higher (95% CI: 1.25-7.55) when mothers had pre and postnatal symptoms, after controlling for breastfeeding status, infant age, antibiotics exposure and other covariates. Postnatal symptoms were not associated with fecal sIgA, independently of breastfeeding status. Infants born to mothers with depressive symptoms appear to have lower fecal sIgA concentrations, predisposing them to higher risk for allergic disease.

Sex-specific impact of asthma during pregnancy on infant gut microbiota.

Asthma during pregnancy is associated with retardation of fetal growth in a sex-specific manner. Lactobacilli microbes influence infant growth. This study aimed to determine whether lactobacilli and other microbes are reduced in the gut of infants born to an asthmatic mother, and whether this differs by the sex of the infant.Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal Development full-term cohort were studied. The abundance of infant faecal microbiota at 3-4 months, profiled by gene sequencing, was compared between both women with and without asthma treatment during pregnancy. Infant sex, maternal ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding status and intrapartum antibiotic treatment were tested as covariates.Independent of birth mode and other covariates, male, Caucasian infants born to women with prenatal asthma harboured fewer lactobacilli in the gut at 3-4 months of age. If asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in males was further reduced in the infant gut, whereas the microbiota of female infants was enriched with Bacteroidaceae Similar differences in infant gut microbial composition according to maternal prenatal asthma status were also more evident among women with food or environmental allergies.Gut lactobacilli were less abundant in male infants, but Bacteroidaceae were more abundant in female infants at 3-4 months of age, following maternal asthma during pregnancy.

Microbial programming of health and disease starts during fetal life.

The pioneer microbiota of the neonatal gut are essential for gut maturation, and metabolic and immunologic programming. Recent research has shown that early bacterial colonization may impact the occurrence of disease later in life (microbial programming). Despite early conflicting evidence, it has long been considered that the womb is a sterile environment and human microbial colonization begins at birth. In the last few years, several findings have reiterated the presence of microbes in infant first stool (meconium) and pointed to the existence of in utero microbial colonization of the infant gut. The dominant bacterial taxa detected in meconium specimens belong to the Enterobacteriaceae family (Escherichia genus) and lactic acid bacteria (notably members of the genera Leuconostoc, Enterococcus, and Lactococcus). Maternal atopy promotes dominance of Enterobacteriaceae in newborn meconium, which in turn may lead to respiratory problems in the infant. This microbial interaction with the host immune system may in fact, originate during fetal life. Our review evaluates the evidence for an intrauterine origin of meconium microbiota, their composition and influences, and potential clinical implications on infant health.

Inulin and fructo-oligosaccharides have divergent effects on colitis and commensal microbiota in HLA-B27 transgenic rats.

Modulation of intestinal microbiota by non-digestible carbohydrates may reduce inflammation in inflammatory bowel disease (IBD). The aim of the present study was to assess the effects of inulin and fructo-oligosaccharides (FOS) on intestinal microbiota and colitis in HLA-B27 transgenic rats, a well-validated rodent model for IBD. In this study, 4-week-old rats were fed 8 g/kg body weight inulin or FOS for 12 weeks, or not. Faeces were collected at 4 and 16 weeks of age; and caecal samples were collected at necropsy. The effects of inulin and FOS on chronic intestinal inflammation were assessed using a gross gut score, histology score and levels of mucosal IL-1ß. Intestinal microbiota were characterised by quantitative PCR and denaturing gradient gel electrophoresis. Colitis was significantly reduced in all FOS-fed rats compared to the control diet, whereas inulin decreased chronic intestinal inflammation in only half the number of animals. Quantitative analysis of caecal microbiota demonstrated that inulin increased the numbers of total bacteria and the Bacteroides-Prevotella-Porphyromonas group, FOS increased bifidobacteria, and both fructans decreased Clostridium cluster XI. In the faecal samples, both inulin and FOS decreased total bacteria, Bacteroides-Prevotella-Porphyromonas group, and Clostridium clusters XI and XIVa. FOS increased Bifidobacterium spp., and mediated a decrease of gene copies of Enterobacteriaceae and Clostridium difficile toxin B in faeces. SCFA concentrations in the faecal and caecal samples were unaffected by the diets. In conclusion, FOS increased the abundance of Bifidobacterium spp., whereas both fructans reduced Clostridium cluster XI and C. difficile toxin gene expression, correlating with a reduction of chronic intestinal inflammation.

Human Milk From Atopic Mothers Has Lower Levels of Short Chain Fatty Acids.

Short chain fatty acids (SFCAs) are microbial metabolites produced in the gut upon fermentation of dietary fiber. These metabolites interact with the host immune system and can elicit epigenetic effects. There is evidence to suggest that SCFAs may play a role in the developmental programming of immune disorders and obesity, though evidence in humans remains sparse. Here we have quantified human milk (HM) SCFA levels in an international cohort of atopic and non-atopic mothers (n = 109). Our results demonstrate that human milk contains detectable levels of the SCFAs acetate, butyrate, and formate. Samples from atopic mothers had significantly lower concentrations of acetate and butyrate than those of non-atopic mothers. HM SCFA levels in atopic and non-atopic women also varied based on maternal country of residence (Australia, Japan, Norway, South Africa, USA). Reduced exposure to HM SCFA in early life may program atopy or overweight risk in breastfed infants.

Worldwide Variation in Human Milk Metabolome: Indicators of Breast Physiology and Maternal Lifestyle?

Human milk provides essential substrates for the optimal growth and development of a breastfed infant. Besides providing nutrients to the infant, human milk also contains metabolites which form an intricate system between maternal lifestyle, such as the mother's diet and the gut microbiome, and infant outcomes. This study investigates the variation of these human milk metabolites from five different countries. Human milk samples (n = 109) were collected one month postpartum from Australia, Japan, the USA, Norway, and South Africa and were analyzed by nuclear magnetic resonance. The partial least squares discriminant analysis (PLS-DA) showed separation between either maternal countries of origin or ethnicities. Variation between countries in concentration of metabolites, such as 2-oxoglutarate, creatine, and glutamine, in human milk, between countries, could provide insights into problems, such as mastitis and/or impaired functions of the mammary glands. Several important markers of milk production, such as lactose, betaine, creatine, glutamate, and glutamine, showed good correlation between each metabolite. This work highlights the importance of milk metabolites with respect to maternal lifestyle and the environment, and also provides the framework for future breastfeeding and microbiome studies in a global context.

The infant gut microbiome: evidence for obesity risk and dietary intervention.

Increasing globally, particularly in children, obesity is a serious public health issue and risk factor for overweight and metabolic disease in later life. Both in experimental animal and human studies, advances in gene sequencing technologies have yielded intriguing possibilities for the role of the gut microbiome in later development of overweight status. Before translating study findings into practice, we must first reconcile inconsistencies between animal experimentation, and human adult and infant studies. Recent evidence for associations with gut microbiota and infant weight gain or child weight status, implicate Bacteroides and Lactobacillus species. Dietary manipulation with human milk and pre/probiotic formulations holds promise for preventing obesity.