Objective
Dysbiosis of the infant gut microbiota may have long‐term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut ...microbiota, and to explore whether breastfeeding modifies these effects.
Design
Prospective pregnancy cohort of Canadian infants born in 2010–2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study.
Setting
General community.
Sample
Representative sub‐sample of 198 healthy term infants from the CHILD Study.
Methods
Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months.
Main outcome measures
Infant gut microbiota profiles.
Results
In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre‐labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon‐specific composition also differed, with the genera Bacteroides and Parabacteroides under‐represented, and Enterococcus and Clostridium over‐represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non‐breastfed infants.
Conclusions
Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations.
Tweetable
Maternal #antibiotics during childbirth alter the infant gut #microbiome.
Tweetable
Maternal #antibiotics during childbirth alter the infant gut #microbiome.
Diapause, the dormancy common to overwintering insects, evokes a unique pattern of gene expression. In the flesh fly, most, but not all, of the fly's heat shock proteins (Hsps) are up-regulated. The ...diapause up-regulated Hsps include two members of the Hsp70 family, one member of the Hsp60 family (TCP-1), at least four members of the small Hsp family, and a small Hsp pseudogene. Expression of an Hsp70 cognate, Hsc70, is uninfluenced by diapause, and Hsp90 is actually down-regulated during diapause, thus diapause differs from common stress responses that elicit synchronous up-regulation of all Hsps. Up-regulation of the Hsps begins at the onset of diapause, persists throughout the overwintering period, and ceases within hours after the fly receives the signal to reinitiate development. The up-regulation of Hsps appears to be common to diapause in species representing diverse insect orders including Diptera, Lepidoptera, Coleoptera, and Hymenoptera as well as in diapauses that occur in different developmental stages (embryo, larva, pupa, adult). Suppressing expression of Hsp23 and Hsp70 in flies by using RNAi did not alter the decision to enter diapause or the duration of diapause, but it had a profound effect on the pupa's ability to survive low temperatures. We thus propose that up-regulation of Hsps during diapause is a major factor contributing to cold-hardiness of overwintering insects.
Summary
Background
The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but ...existing evidence is limited and conflicting.
Objective
To explore associations of infant gut microbiota and food sensitization.
Methods
Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population‐based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing.
Results
Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food‐sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23–0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07–3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae.
Conclusions and Clinical Relevance
Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.
Extreme global warming and environmental changes associated with the Toarcian (Lower Jurassic) Oceanic Anoxic Event (T-OAE, ~183 Mya) profoundly impacted marine organisms and terrestrial plants. ...Despite the exceptionally elevated abundances of fossil insects from strata of this age, only assemblages from Germany and Luxembourg have been studied in detail. Here, we focus on the insect assemblage found in strata recording the T-OAE at Alderton Hill, Gloucestershire, UK, where <15% of specimens have previously been described. We located all known fossil insects (n = 370) from Alderton Hill, and used these to create the first comprehensive taxonomic and taphonomic analysis of the entire assemblage. We show that a diverse palaeoentomofaunal assemblage is preserved, comprising 12 orders, 21 families, 23 genera and 21 species. Fossil disarticulation is consistent with insect decay studies. The number of orders is comparable with present-day assemblages from similar latitudes (30°-40°N), including the Azores, and suggests that the palaeoentomofauna reflects a life assemblage. At Alderton, Hemiptera, Coleoptera and Orthoptera are the commonest (56.1%) orders. The high abundance of Hemiptera (22.1%) and Orthoptera (13.4%) indicates well-vegetated islands, while floral changes related to the T-OAE may be responsible for hemipteran diversification. Predatory insects are relatively abundant (~10% of the total assemblage) and we hypothesise that the co-occurrence of fish and insects within the T-OAE represents a jubilee-like event. The marginally higher proportion of sclerotised taxa compared to present-day insect assemblages possibly indicates adaptation to environmental conditions or taphonomic bias. The coeval palaeoentomofauna from Strawberry Bank, Somerset is less diverse (9 orders, 12 families, 6 genera, 3 species) and is taphonomically biased. The Alderton Hill palaeoentomofauna is interpreted to be the best-preserved and most representative insect assemblage from Toarcian strata in the UK. This study provides an essential first step towards understanding the likely influence of the T-OAE on insects.
Chronic HBV infection is a global public health burden estimated to impact nearly 300 million persons worldwide. Despite the advent of potent antiviral agents that effectively suppress viral ...replication, HBV cure remains difficult to achieve because of the persistence of covalently closed circular DNA (cccDNA), HBV‐DNA integration into the host genome, and impaired immune response. Indefinite treatment is necessary for most patients to maintain level of viral suppression. The success of direct‐acting antivirals (DAAs) for hepatitis C treatment has rejuvenated the search for a cure for chronic hepatitis B (CHB), though an HBV cure likely requires an additional layer: immunomodulators for restoration of robust immune responses. DAAs such as entry inhibitors, capsid assembly modulators, inhibitors of subviral particle release, cccDNA silencers, and RNA interference molecules have reached clinical development. Immunomodulators, namely innate immunomodulators (Toll‐like receptor agonists), therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also progressing toward clinical development. The future of the HBV cure possibly lies in triple combination therapies with concerted action on replication inhibition, antigen reduction, and immune stimulation. Many obstacles remain, such as overcoming translational failures, choosing the right endpoint using the right biomarkers, and leveraging current treatments in combination regimens to enhance response rates. This review gives an overview of the current therapies for CHB, HBV biomarkers used to evaluate treatment response, and development of DAAs and immune‐targeting drugs and discusses the limitations and unanswered questions on the journey to an HBV cure.
Highlights • We provide evidence supporting pre- and intra-operative management of patients undergoing gynecologic/oncology surgery. • This guideline will help integrate knowledge into practice, ...align perioperative care, and encourage future investigations.
Highlights • We provide evidence supporting postoperative management of patients undergoing gynecologic/oncology surgery. • This guideline will help integrate knowledge into practice, align ...perioperative care, and encourage future investigations.
Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic ...metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.
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