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Breast milk components contribute to the infant’s immune development and protection, and among other immune factors, immunoglobulins (Igs) are the most studied. The presence of IgA in milk has been known for a long time; however, less information is available about the presence of other Igs such as IgM, IgG, and their subtypes (IgG1, IgG2, IgG3, and IgG4) or even IgE or IgD. The total Ig concentration and profile will change during the course of lactation; however, there is a great variability among studies due to several variables that limit establishing a clear pattern. In this context, the aim of this review was firstly to shed light on the Ig concentration in breast milk based on scientific evidence and secondly to study the main factors contributing to such variability. A search strategy provided only 75 studies with the prespecified eligibility criteria. The concentrations and proportions found have been established based on the intrinsic factors of the study—such as the sampling time and quantification technique—as well as participant-dependent factors, such as lifestyle and environment. All these factors contribute to the variability of the immunoglobulinome described in the literature and should be carefully addressed for further well-designed studies and data interpretation.

Background Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been carried out. Results Here, we leverage metagenomic assembly followed by a reference-based binning strategy to screen over 6500 gut metagenomes spanning geography and lifestyle and reconstruct over 1300 E. rectale high-quality genomes from metagenomes. We extend previous results of biogeographic stratification, identifying a new subspecies predominantly found in African individuals and showing that closely related non-human primates do not harbor E. rectale . Comparison of pairwise genetic and geographic distances between subspecies suggests that isolation by distance and co-dispersal with human populations might have contributed to shaping the contemporary population structure of E. rectale . We confirm that a relatively recently diverged E. rectale subspecies specific to Europe consistently lacks motility operons and that it is immotile in vitro, probably due to ancestral genetic loss. The same subspecies exhibits expansion of its carbohydrate metabolism gene repertoire including the acquisition of a genomic island strongly enriched in glycosyltransferase genes involved in exopolysaccharide synthesis. Conclusions Our study provides new insights into the population structure and ecology of E. rectale and shows that shotgun metagenomes can enable population genomics studies of microbiota members at a resolution and scale previously attainable only by extensive isolate sequencing.

Cognitive decline, obesity and gut dysfunction or microbial dysbiosis occur in association. Our aim was to identify gut microbiota-metabolomics signatures preceding dementia in genetically prone (3xtg) mice, with and without superimposed high-fat diet. We examined the composition and diversity of their gut microbiota, and serum and faecal metabolites. 3xtg mice showed brain hypometabolism typical of pre-demented stage, and lacked the physiological bacterial diversity between caecum and colon seen in controls. Cluster analyses revealed distinct profiles of microbiota, and serum and fecal metabolome across groups. Elevation in Firmicutes-to-Bacteroidetes abundance, and exclusive presence of Turicibacteraceae , Christensenellaceae , Anaeroplasmataceae and Ruminococcaceae , and lack of Bifidobacteriaceae , were also observed. Metabolome analysis revealed a deficiency in unsaturated fatty acids and choline, and an overabundance in ketone bodies, lactate, amino acids, TMA and TMAO in 3xtg mice, with additive effects of high-fat diet. These metabolic alterations were correlated with high prevalence of Enterococcaceae , Staphylococcus , Roseburia , Coprobacillus and Dorea , and low prevalence of S24.7 , rc4.4 and Bifidobacterium , which in turn related to cognitive impairment and cerebral hypometabolism. Our results indicate an effect of transgenic background on gut microbiome-metabolome, enhanced by high-fat diet. The resulting profiles may precede overt cognitive impairment, suggesting their predictive or risk-stratifying potential.

The obesity epidemic is a global challenge, and the velocity of propagation is high in the population at reproductive age. Overweight and obesity during pregnancy have been associated with high birth weight and an increased risk of childhood obesity, reinforcing the risk of other non-communicable diseases. Obesity involves chronic low-grade systemic inflammation. New biomarkers for early detection of obesity risk are urgently required. The aim of this study was to identify the connection between pregestational BMI (pre-BMI) status and inflammatory biomarkers during the third trimester of pregnancy and their association with intestinal microbiota composition. Fifty-four pregnant women were classified according to pre-pregnancy BMI as normoweight, overweight, or obese. Weight gain, inflammatory biomarkers (hs_CRP, haptoglobin, and suPAR), and microbiota composition were assessed during the third trimester. A significant lower weight gain for obese mothers and a positive correlation between pre-BMI and inflammatory biomarkers were detected (Spearman's correlation). Haptoglobin levels were significantly higher in overweight and obese mothers. Higher Firmicutes levels and a higher ratio Firmicutes/Bacteroidetes were observed in the overweight and obese subjects. High hs_CRP and haptoglobin levels were also correlated with decreased microbiota diversity (Shannon index), whereas haptoglobin and hs_CRP values were correlated with several microbiota components, such as Ruminococcus gnavus and Faecalibacterium, and with specific phyla in the normoweight and overweight mothers; no significant associations with microbiota were found for suPAR. In conclusion, haptoglobin and hs_CRP reflected pregestational BMI status and related microbiota components, but haptoglobin was a better biomarker for microbiota associated with overweight. suPAR was associated with low grade inflammation dependent on pre-pregnancy BMI, but it was not related to deviated microbiota profiles.

Host genetic factors, such as histo-blood group antigens (HBGAs), are associated with susceptibility to norovirus (NoV) and rotavirus (RV) infections. Recent advances point to the gut microbiome as a key player necessary for a viral pathogen to cause infection. In vitro NoV attachment to host cells and resulting infections have been linked to interactions with certain bacterial types in the gut microbiota. We investigated the relationship between host genotype, gut microbiota, and viral infections. Saliva and fecal samples from 35 adult volunteers were analysed for secretor status genotype, the gut microbiota composition by 16S rRNA gene sequencing, and salivary IgA titers to NoV and RV. Higher levels of IgA against NoV and RV were related to secretor-positive status. No significant differences were found between the FUT2 genotype groups, although the multivariate analysis showed a significant impact of host genotype on specific viral susceptibilities in the microbiome composition. A specific link was found between the abundance of certain bacterial groups, such as Faecalibacterium and Ruminococcus spp., and lower IgA titers against NoV and RV. As a conclusion, we can state that there is a link between host genetics, gut microbiota, and susceptibility to viral infections in humans.

Background: Early host-microbe interaction provides important maturational stimuli for the developing immune system. The role of prenatal microbial contact remains elusive. Objectives: Our aim was to investigate whether microbes in placenta or amniotic fluid affect fetal innate immune gene expression during late pregnancy and whether innate immune gene expression profiles in the placenta and the fetal gut may be modulated by dietary supplementation with specific probiotics. Methods: Altogether 43 pregnant women were randomized to receive (1) Bifidobacterium lactis, (2) B. lactis in combination with Lactobacillus rhamnosus GG (LGG) or (3) placebo for 14 days before elective cesarian section at full term in a double-blind clinical trial. Bacteria in amniotic fluid and placenta were detected by quantitative (q)PCR. The expression of Toll-like receptor (TLR)-related genes in the placenta and meconium samples was assessed by qPCR. Gene expression patterns in meconium were interpreted to reflect immune physiology in the fetal gut. Results: The study was completed by 29 mother-infant pairs. Bacterial DNA was detected in all placenta samples. Microbial DNA in amniotic fluid and placenta was associated with changes in TLR-related gene expression in the fetal intestine. Maternal probiotic supplementation significantly modulated the expression of TLR-related genes both in the placenta and in the fetal gut. Conclusions: Microbial contact in utero is associated with changes in fetal intestinal innate immune gene expression profile. Fetal and placental immune physiology may be modulated by maternal dietary intervention using specific probiotics.

Selenium is a well-known essential element with important roles in human reproductive health mainly due to its antioxidant character. This study aimed to investigate the potential role of selenoproteins on gut microbiota and male reproductive health. A new assay for the absolute quantification of selenoproteins in testicular tissue based on two dimensional chromatography with inductively coupled plasma mass spectrometry was performed for the first time. The gut microbiota profile was obtained by 16S rRNA gene sequencing. Numerous associations were found between testicular selenoproteins and gut microbiota (e.g. Mucispirillum , related with sperm activity and testosterone, was associated with glutathione peroxidase (GPx) and selenoalbumin (SeAlb), while Escherichia/Shigella , related to sex hormones, correlated with GPx, selenoprotein P (SelP) and SeAlb). The effects of Se-supplementation on testicular selenoproteins only occur in conventional mice, suggesting a potential selenoproteins-microbiota interplay that underlies testicular function. The selenoproteins GPx and SelP have been quantified for the first time in the testicles, and the novel identification of SeAlb, a protein with nonspecifically incorporated Se, is also reported. These findings demonstrate the significant impact of Se-supplementation on gut microbiota and male reproductive health. In addition, the analytical methodology applied here in selenoprotein quantification in testicular tissue opens new possibilities to evaluate their role in gut microbiota and reproductive health axis.

We investigated the association between bacterial microbiota in breast milk and the infant mouth. The influence of human papilloma virus (HPV) infection on infant oral microbiota was also assessed. Altogether 35 breast milk and 35 infant oral samples with known HPV status were selected from the Finnish Family HPV Study cohort. In total, there were 31 mother-infant pairs. The microbiota composition was characterized by 16S rRNA gene sequencing (V3-V4 region). HPV DNA was present in 8.6% (3/35) of the breast milk and 40% (14/35) of the infant oral samples. Eight shared genera between breast milk and infant oral were found; these included Streptococcus, Staphylococcus, Unclassified Gemellaceae, Rothia, Veillonella, Haemophilus, Propionibacterium and Corynebacterium. HPV status was not associated with either microbiota richness or diversity in the infant mouth. However, the infant oral microbiota clustered in different groups according to HPV status. We detected higher abundance of Veillonella dispar (p = 0.048) at species level in HPV negative infant oral samples. We did not detect differences in the breast milk microbiota composition related to HPV infection due to only three HPV positive milk samples. HPV infection is associated with distinct oral bacterial microbiota composition in infants. The direction of causality underlying the phenomenon remains unclear.

The host microbiota has emerged a third player in interactions between hosts and viral pathogens. This opens new possibilities to use different tools to modulate the intestinal microbial composition, aimed at reducing the risk of or treating viral enteric infections.

Background Breast milk is a vehicle to transfer protective antibodies from the lactating mother to the neonate. After SARS-CoV-2 infection, virus-specific IgA and IgG have been identified in breast milk, however, there are limited data on the impact of different COVID-19 vaccine types in lactating women. This study is aimed to evaluate the time course of induction of SARS-CoV-2-specific IgA and IgG in breast milk after vaccination. Methods In this prospective observational study in Spain, 86 lactating women from priority groups receiving the vaccination against SARS-CoV-2 were included. Breast milk samples were collected longitudinally at seven or eight-time points (depending on vaccine type). A group with confirmed SARS-CoV-2 infection ( n =19) and a group of women from pre-pandemic time ( n =20) were included for comparison. Results Eighty-six vaccinated lactating women [mean age, 34.6 ± 3.7 years] of whom 96% were Caucasian and 92% were healthcare workers. A total number of 582 milk samples were included, and vaccine distribution was BioNTech/Pfizer (BNT162b2, n =34), Moderna (mRNA-1273, n =20), and AstraZeneca (ChAdOx1 nCoV-19, n =32). For each vaccine, 7 and 8 longitudinal time points were collected from baseline up to 30 days after the second dose for mRNA vaccines and adenovirus-vectored vaccines, respectively. A strong reactivity was observed for IgG and IgA after vaccination mainly after the 2 nd dose. The presence and persistence of specific SARS-CoV-2 antibodies in breast milk were dependent on the vaccine type, with higher IgG and IgA levels in mRNA-based vaccines when compared to AstraZeneca, and on previous virus exposure. High intra- and inter-variability were observed, being relevant for IgA antibodies. In milk from vaccinated women, anti-SARS-CoV-2 IgG was significantly higher while IgA levels were lower than in milk from COVID-19-infected women. Women with previous COVID-19 increased their IgG antibodies levels after the first dose to a similar level observed in vaccinated women after the second dose. Conclusions COVID-19 vaccination induced anti-SARS-CoV-2 IgA and IgG in breast milk with higher levels after the 2 nd dose. Levels of anti-SARS-CoV-2 IgA and IgG are dependent on the vaccine type. Further studies are warranted to demonstrate the protective antibody effect against COVID-19 in infants from vaccinated and infected mothers. Trial registration NCT04751734 (date of registration is on February 12, 2021)