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Previous studies on the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants have provided highly variable results. Here we perform a meta-analysis of seven microbiome studies (1825 stool samples from 684 infants) to compare the gut microbiota of non-EBF and EBF infants across populations. In the first 6 months of life, gut bacterial diversity, microbiota age, relative abundances of Bacteroidetes and Firmicutes, and predicted microbial pathways related to carbohydrate metabolism are consistently higher in non-EBF than in EBF infants, whereas relative abundances of pathways related to lipid metabolism, vitamin metabolism, and detoxification are lower. Variation in predicted microbial pathways associated with non-EBF infants is larger among infants born by Caesarian section than among those vaginally delivered. Longer duration of exclusive breastfeeding is associated with reduced diarrhea-related gut microbiota dysbiosis. Furthermore, differences in gut microbiota between EBF and non-EBF infants persist after 6 months of age. Our findings elucidate some mechanisms of short and long-term benefits of exclusive breastfeeding across different populations. Studies on the effects of breastfeeding on the infant gut microbiota have provided inconsistent results. Here, Ho et al. perform a meta-analysis of seven studies across different populations, supporting that exclusive breastfeeding is associated with short-term and long-term alterations in the infant gut microbiota.

Background Symbiotic relationships between animals and bacteria have profound impacts on the evolutionary trajectories of each partner. Animals and gut bacteria engage in a variety of relationships, occasionally persisting over evolutionary timescales. Ants are a diverse group of animals that engage in many types of associations with taxonomically distinct groups of bacterial associates. Here, we bring into culture and characterize two closely-related strains of gut associated Acetobacteraceae (AAB) of the red carpenter ant, Camponotus chromaiodes . Results Genome sequencing, assembly, and annotation of both strains delineate stark patterns of genomic erosion and sequence divergence in gut associated AAB. We found widespread horizontal gene transfer (HGT) in these bacterial associates and report elevated gene acquisition associated with energy production and conversion, amino acid and coenzyme transport and metabolism, defense mechanisms, and lysine export. Both strains have acquired the complete NADH-quinone oxidoreductase complex, plausibly from an Enterobacteriaceae origin, likely facilitating energy production under diverse conditions. Conservation of several lysine biosynthetic and salvage pathways and accumulation of lysine export genes via HGT implicate L-lysine supplementation by both strains as a potential functional benefit for the host. These trends are contrasted by genome-wide erosion of several amino acid biosynthetic pathways and pathways in central metabolism. We perform phylogenomic analyses on both strains as well as several free living and host associated AAB. Based on their monophyly and deep divergence from other AAB, these C. chromaiodes gut associates may represent a novel genus. Together, our results demonstrate how extensive horizontal transfer between gut associates along with genome-wide deletions leads to mosaic metabolic pathways . More broadly, these patterns demonstrate that HGT and genomic erosion shape metabolic capabilities of persistent gut associates and influence their genomic evolution. Conclusions Using comparative genomics, our study reveals substantial changes in genomic content in persistent associates of the insect gastrointestinal tract and provides evidence for the evolutionary pressures inherent to this environment. We describe patterns of genomic erosion and horizontal acquisition that result in mosaic metabolic pathways. Accordingly, the phylogenetic position of both strains of these associates form a divergent, monophyletic clade sister to gut associates of honey bees and more distantly to Gluconobacter.

Background Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery. Results In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells. Conclusion Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.

Background Infants exposed to HIV but uninfected have altered immune profiles which include heightened systemic inflammation. The mechanism(s) underlying this phenomenon is unknown. Here, we investigated differences in neonatal gut bacterial and viral microbiome and associations with inflammatory biomarkers in plasma. Further, we tested whether HIV exposure impacts antibody-microbiota binding in neonatal gut and whether antibodies in breast milk impact the growth of commensal bacteria. Results Neonates exposed to HIV but uninfected (nHEU) exhibited altered gut bacteriome and virome compared to unexposed neonates (nHU). In addition, HIV exposure differentially impacted IgA-microbiota binding in neonates. The relative abundance of Blautia spp. in the whole stool or IgA-bound microbiota was positively associated with plasma concentrations of C-reactive protein. Finally, IgA from the breast milk of mothers living with HIV displayed a significantly lower ability to inhibit the growth of Blautia coccoides which was associated with inflammation in nHEU. Conclusion nHEU exhibits profound alterations in gut bacterial microbiota with a mild impact on the enteric DNA virome. Elevated inflammation in nHEU could be due to a lower capacity of breast milk IgA from mothers living with HIV to limit growth the of gut bacteria associated with inflammation. BDUn311MBkuDfDvveFNavE Video Abstract

Effective contraceptives are a global health imperative for reproductive-aged women. However, there remains a lack of rigorous data regarding the effects of contraceptive options on vaginal bacteria and inflammation. Among 218 women enrolled into a substudy of the ECHO Trial (NCT02550067), we evaluate the effect of injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG), and a copper intrauterine device (Cu-IUD) on the vaginal environment after one and six consecutive months of use, using 16S rRNA gene sequencing and multiplex cytokine assays. Primary endpoints include incident BV occurrence, bacterial diversity, and bacterial and cytokine concentrations. Secondary endpoints are bacterial and cytokine concentrations associated with later HIV seroconversion. Participants randomized to Cu-IUD exhibit elevated bacterial diversity, increased cytokine concentrations, and decreased relative abundance of lactobacilli after one and six months of use, relative to enrollment and other contraceptive options. Total bacterial loads of women using Cu-IUD increase 5.5 fold after six months, predominantly driven by increases in the concentrations of several inflammatory anaerobes. Furthermore, growth of L. crispatus (MV-1A-US) is inhibited by Cu 2+ ions below biologically relevant concentrations, in vitro. Our work illustrates deleterious effects on the vaginal environment induced by Cu-IUD initiation, which may adversely impact sexual and reproductive health. Here, in a randomized trial, the authors comparatively evaluate the effect of a copper intrauterine device versus other contraceptive options on the vaginal environment after one and six consecutive months of use, finding to exert changes on the vaginal microbiota that may potentially lead to detrimental sex and reproductive health.

Cervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives. We collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis. Cytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota. Both DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.

Background Symbiotic associations between gut microbiota and their animal hosts shape the evolutionary trajectories of both partners. The genomic consequences of these relationships are significantly influenced by a variety of factors, including niche localization, interaction potential, and symbiont transmission mode. In eusocial insect hosts, socially transmitted gut microbiota may represent an intermediate point between free living or environmentally acquired bacteria and those with strict host association and maternal transmission. Results We characterized the bacterial communities associated with an abundant ant species, Camponotus chromaiodes . While many bacteria had sporadic distributions, some taxa were abundant and persistent within and across ant colonies. Specially, two Acetobacteraceae operational taxonomic units (OTUs; referred to as AAB1 and AAB2) were abundant and widespread across host samples. Dissection experiments confirmed that AAB1 and AAB2 occur in C. chromaiodes gut tracts. We explored the distribution and evolution of these Acetobacteraceae OTUs in more depth. We found that Camponotus hosts representing different species and geographical regions possess close relatives of the Acetobacteraceae OTUs detected in C. chromaiodes . Phylogenetic analysis revealed that AAB1 and AAB2 join other ant associates in a monophyletic clade. This clade consists of Acetobacteraceae from three ant tribes, including a third, basal lineage associated with Attine ants. This ant-specific AAB clade exhibits a significant acceleration of substitution rates at the 16S rDNA gene and elevated AT content. Substitutions along 16S rRNA in AAB1 and AAB2 result in ~10 % reduction in the predicted rRNA stability. Conclusions Combined, these patterns in Camponotus -associated Acetobacteraceae resemble those found in cospeciating gut associates that are both socially and maternally transmitted. These associates may represent an intermediate point along an evolutionary trajectory manifest most extremely in symbionts with strict maternal transmission. Collectively, these results suggest that Acetobacteraceae may be a frequent and persistent gut associate in Camponotus species and perhaps other ant groups, and that its evolution is strongly impacted by this host association.

South African infants were followed longitudinally to interrogate mechanism for lower human immunodeficiency virus (HIV) transmission with exclusive breastfeeding. Our findings suggest that gut microbiota of exclusively breastfed infants is associated with low peripheral T-cell and mucosal immune activation. Abstract Background Exclusive breastfeeding reduces the rate of postnatal human immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding; however, the mechanisms of this protection are unknown. Our study aimed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding. Methods We performed a prospective, longitudinal study of infants from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the role of any non-breast milk feeds, excluding prescribed medicines on stool microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation via flow cytometry, and buccal mucosal gene expression via quantitative polymerase chain reaction assay. Results A total of 155 infants were recruited at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg. All infants were exclusively breastfed (EBF) at birth, but only 43.5% and 20% remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool microbial diversity and distinct microbial composition in exclusively breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T-cell activation, which was lower in EBF infants. In the oral mucosa, gene expression of chemokine and chemokine receptors involved in recruitment of HIV target cells to tissues, as well as epithelial cytoskeletal proteins, was lower in EBF infants. Conclusions These data suggest that nonexclusive breastfeeding alters the gut microbiota, increasing T-cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in EBF infants.

The switching properties of most liquid-crystal electro-optic devices rely mainly on the reorientation of the average molecular direction (director) within the bulk of the liquid-crystal layer 1 . Reorientation of the director at or near the surfaces of the layer usually has an insignificant effect on device performance. Here we describe a different configuration in which a nematic liquid crystal is placed between a flat surface treated to induce a parallel anchoring of the director and a grating surface treated to give a perpendicular anchoring. We show that this configuration leads to an effective azimuthal anchoring at the grating surface that depends on the applied voltage when the nematic phase has negative dielectric anisotropy (that is, the director has a tendency to align perpendicular to the applied field). This leads to a voltage-controlled twist effect in the liquid-crystal cell that is highly sensitive to the grating profile. Furthermore, this twist effect possesses an electro-optic response which is far less dependent on viewing angle compared to many other liquid-crystal display configurations. We therefore suggest that this technology might find application in the next generation of liquid-crystal displays.

Current nematic liquid-crystal (LC) displays rely on voltage-induced reorientation of the director (the average molecular direction) within the bulk of the LC layer. In these devices, the surface region of the LC is strongly anchored to the cell walls and does not undergo reorientation at normal operating voltages. This situation is not optimal and indeed modelling has shown that weak anchoring of the LC can in principle lead to lower operating voltages and improved steepness in the electro-optic response 1 . Achieving weak anchoring in practice has proved difficult. Soft rubbing of a polymer 2 or photoinduced ordering of a polymer 3 coating the cell walls can lead to weak azimuthal (in-plane) anchoring, but a memory effect is still present which prevents high-speed surface reorientation. Some surface treatments, such as obliquely evaporated silicon oxide, can also induce weak anchoring, but only for a restricted range of temperatures 4 , 5 . Here we report a different approach to weak anchoring, which relies on the addition of small percentages of oligomeric molecules to the LC. This approach results in very small zenithal (out ofsubstrate plane) and azimuthal (in plane) anchoring energies. When applied to nematic displays, such treatments lead to a halving of the operating voltage.