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The gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia , Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

We describe a severe form of congenital myasthenic syndrome (CMS) caused by two heteroallelic mutations: a nonsense and a missense mutation in the gene encoding agrin (AGRN). The identified mutations, Q353X and V1727F , are located at the N-terminal and at the second laminin G-like (LG2) domain of agrin, respectively. A motor-point muscle biopsy demonstrated severe disruption of the architecture of the neuromuscular junction (NMJ), including: dispersion and fragmentation of endplate areas with normal expression of acetylcholinesterase; simplification of postsynaptic membranes; pronounced reduction of the axon terminal size; widening of the primary synaptic cleft; and, collection of membranous debris material in the primary synaptic cleft and in the subsynaptic cytoplasm. Expression studies in heterologous cells revealed that the Q353X mutation abolished expression of full-length agrin. Moreover, the V1727F mutation decreased agrin-induced clustering of the acetylcholine receptor (AChR) in cultured C2 muscle cells by >100-fold, and phosphorylation of the MuSK receptor and AChR beta subunit by ~tenfold. Surprisingly, the V1727F mutant also displayed increased binding to α-dystroglycan but decreased binding to a neural (z+) agrin-specific antibody. Our findings demonstrate that agrin mutations can associate with a severe form of CMS and cause profound distortion of the architecture and function of the NMJ. The impaired ability of V1727F agrin to activate MuSK and cluster AChRs, together with its increased affinity to α-dystroglycan, mimics non-neural (z−) agrin and are important determinants of the pathogenesis of the disease.

Lactogenesis stage II, also known as when a mother's milk “comes in”, is characterised by copious milk production. Delayed lactogenesis II, when onset occurs after 72 hours post-partum, has been linked to early breastfeeding cessation. It has been suggested that caesarean section is a risk factor for late onset of lactogenesis II. It is unknown why lactogenesis II may be delayed in caesarean section but there are several potential reasons such as volume of blood loss, maternal stress, delayed breastfeeding initiation and difficulties with mobility and positioning. Analysis of timing of lactogenesis and breastfeeding frequency was carried out on data from the PROMESA and IMPRINT studies, which were looking at the supplementation of breast milk with a probiotic Bifidobacterium infantis. IMPRINT was carried out in California and enrolled eighty women prior to birth or before postnatal day 4. The PROMESA study in the UK only recruited women who were booked for elective caesarean sections, and also enrolled eighty mother-baby dyads. As part of both studies mothers filled out a variety of surveys and daily logs, including a daily feeding log, along with self-reported lactogenesis. Using logistic regression, we looked at whether mode of birth (spontaneous vaginal delivery, emergency and elective caesarean section) was associated with the timing of onset of lactogenesis, and linear regression to look at the difference in breastfeeding frequency between modes of birth. Mode of birth was significantly associated with delayed onset of lactogenesis > 3 days (OR 3.38, 95% CI 2.48–4.61). There was also a reduced frequency of breastfeeding in the first week post-partum in mother-baby dyads who underwent an elective caesarean section. These findings suggest that mothers who give birth by elective caesarean section may need additional support with breastfeeding in the early days post-partum, as well as ongoing support long-term to reduce the likelihood of early cessation of breastfeeding.