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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.

Severe acute malnutrition (SAM) is a major global public health problem. We aimed to assess the effects of probiotic and synbiotic supplementation on rate of weight gain and change in length in young SAM infants. This study was substudy of a single-blind randomized clinical trial (NCT0366657). During nutritional rehabilitation, 67 <6 months old SAM infants were enrolled and randomized to receive either probiotic ( Bifidobacterium. infantis EVC001) or synbiotic ( B. infantis EVC001 + Lacto-N-neotetraose [LNnT]) or placebo (Lactose) for four weeks and were followed for four more weeks after supplementation. In multivariable linear regression model, the mean rate of weight gain in the probiotic arm compared to placebo was higher by 2.03 unit (P < 0.001), and 1.13 unit (P = 0.030) in the synbiotic arm. In linear mixed-effects model, mean WAZ was higher by 0.57 unit (P = 0.018) in probiotic arm compared to placebo. Although not statistically significant, delta length for age z score (LAZ) trended to be higher among children in probiotc (β = 0.25) and synbiotic (β = 0.26) arms compared to placebo in multivariable linear regression model. Our study describes that young SAM infants had a higher rate of weight gain when supplemented with probiotic alone, compared to their counterparts with either synbiotic or placebo.

Human milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of < 6 months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers’ breastmilk may have a negative impact on young infants’ nutritional status.

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

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.