represents an important early life microbiota member. Specific bifidobacterial components, exopolysaccharides (EPS), positively modulate host responses, with purified EPS also suggested to impact ...microbe-microbe interactions by acting as a nutrient substrate. Thus, we determined the longitudinal effects of bifidobacterial EPS on microbial communities and metabolite profiles using an infant model colon system.
Differential gene expression and growth characteristics were determined for each strain;
UCC2003 and corresponding isogenic EPS-deletion mutant (
UCC2003del). Model colon vessels were inoculated with
and microbiome dynamics monitored using 16S rRNA sequencing and metabolomics (NMR).
Transcriptomics of EPS mutant vs.
UCC2003 highlighted discrete differential gene expression (e.g.,
biosynthetic cluster), though overall growth dynamics between strains were unaffected. The EPS-positive vessel had significant shifts in microbiome and metabolite profiles until study end (405 h); with increases of
and
, and short-chain fatty acids, with further correlations between taxa and metabolites which were not observed within the EPS-negative vessel.
These data indicate that
UCC2003 EPS is potentially metabolized by infant microbiota members, leading to differential microbial metabolism and altered metabolite by-products. Overall, these findings may allow development of EPS-specific strategies to promote infant health.
Background
There is near‐global consensus that all newborns be given parenteral vitamin K1 (VK1) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and ...cases of late VKDB are reported in exclusively breastmilk‐fed preterm infants despite VK prophylaxis at birth.
Objectives
To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under‐γ‐carboxylated (Glu) species of Gla proteins, factor II (PIVKA‐II), and osteocalcin (GluOC), synthesized by liver and bone, respectively.
Patients/Methods
Prospective, multicenter, observational study in preterm infants born <33 weeks' gestation. Blood samples and dietary history were collected before hospital discharge, and after discharge at 2–3 months’ corrected age. Outcome measures were serum VK1, PIVKA‐II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk‐fed and formula/mixed‐fed infants after discharge.
Results
After discharge, breastmilk‐fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA‐II (0.10 vs. 0.02 AU/ml) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed‐feed diet. Pre‐discharge (based on elevated PIVKA‐II), only one (2%) of 45 breastmilk‐fed infants was VK insufficient. After discharge, eight (67%) of 12 exclusively breastmilk‐fed babies were VK insufficient versus only one (4%) of 25 formula/mixed‐fed babies.
Conclusions
Preterm infants who remain exclusively or predominantly human breastmilk‐fed after neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine postdischarge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency.
Two novel bacterial isolates were cultured from faecal samples of patients attending the Breast Care clinic at the Norwich and Norfolk University Hospital. Strain LH1062
was isolated from a ...58-year-old female diagnosed with invasive adenocarcinoma with ductal carcinoma
. Strain LH1063
was isolated from a healthy 51-year-old female. Isolate LH1062
was predicted to be a potential novel genus most closely related to
, whilst LH1063
was predicted to be a novel species belonging to
. Both strains were characterized by polyphasic approaches including 16S rRNA gene analysis, core-genome analysis, average nucleotide identity (ANI) comparisons and phenotypic analysis. Initial screening of the 16S rRNA gene of LH1062
returned a nucleotide identity of 93.4 % to
. For LH1063
, nucleotide identity was a 92.6 % to
. Further investigations showed that LH1062
had a genome size of 2.9 Mb and G+C content of 31.3 mol %. LH1063
had a genome size of 3.3Mb and G+C content of 39.2 mol %. Digital DNA-DNA hybridization (dDDH) and ANI values of LH1062
with its closest relative,
JCM 10604
, were 20.9 and 79.54 %, respectively. For LH1063
, the dDDH and ANI values with its closest relative,
177
, were 19.3 and 77.81 %, respectively. Phenotypic testing confirmed that LH1062
could not be matched to a known validly published isolate in any database; thereby indicating a novel genus for which the name
gen. nov. is now proposed with LH1062
(=DSM 114537
=NCTC 14686
) being the type strain of the proposed novel species
sp. nov. Strain LH1063
(=DSM 114538
=NCTC 14698
) fits within the genus
and, it being the third species within this genus, the name
sp. nov. is proposed.
Abstract
In children exposed to poor hygiene and sanitation, invasion of the gut by pathogenic microbes can result in a subclinical enteropathy termed “environmental enteric dysfunction” (EED) that ...contributes to undernutrition, growth faltering, and impaired organ development. EED may already be present by age 6–12 weeks; therefore, interventions that can be started early in life, and used alongside breastfeeding, are needed to prevent or ameliorate EED. A healthy gut microbiota is critical for intestinal development and repair, nutrient digestion and absorption, and resisting colonization or overgrowth by pathogens. However, its development can be impaired by several environmental factors. Dietary supplementation with pro-, pre-, or synbiotics may be a pragmatic and safe means of building the resilience of the developing gut microbiota against adverse environmental factors, thereby preventing EED.
Malnutrition amongst under-fives remains common in resource-poor countries and is resistant to current interventions. New opportunities have emerged to target "environmental enteric dysfunction" ...(EED) that refers to the abnormal gut structure and function that results from colonisation of the gut with pathogenic microbes and compromises nutrition and growth in early life. Although the gut microbiome may provide a defence against ingested gut pathogens through colonisation resistance, its development is adversely affected by multiple environmental factors. Dietary supplements of pro- or synbiotics may build the resilience of the gut microbiome against these environmental factors and boost colonisation resistance. We aim to assess whether dietary supplementation of newborns in rural Kenya with pro/synbiotics prevents or ameliorates EED and improves growth.
Six hundred newborns less than 4 days old will be recruited from Homa Bay County Teaching and Referral Hospital, western Kenya. Newborns will be randomly allocated, stratified by HIV exposure, in a 1:1:1:1 ratio to one of 4 study arms to receive either of two synbiotics, a probiotic or no supplement. Supplements will be given daily for 10 days and then weekly until 6 months of age. Participants will be followed until the age of 2 years. The primary outcome is systemic inflammation at 6 months assessed by plasma alpha-1-acid glycoprotein. Secondary outcomes include biomarkers of gut health and growth, anthropometric indices, morbidity and mortality.
As dietary supplements with pro- or synbiotics may improve gut health and can be administered in early life, our findings may inform the package of interventions to prevent malnutrition and improve growth in Africa and similar low-resource settings.
Pan African Clinical Trials Registry, Trial number: PACTR202003893276712. Date: 02/03/2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798.
Human breast milk (HBM) is the main source of nutrition for neonates across the critical early-life developmental period. The highest demand for energy is due to rapid neurophysiological expansion ...post-delivery, which is largely met by human milk lipids (HMLs). These HMLs also play a prebiotic role and potentially promote the growth of certain commensal bacteria, which, via HML digestion, supports the additional transfer of energy to the infant. In tandem, HMLs can also exert bactericidal effects against a variety of opportunistic pathogens, which contributes to overall colonisation resistance. Such interactions are pivotal for sustaining homeostatic relationships between microorganisms and their hosts. However, the underlying molecular mechanisms governing these interactions remain poorly understood. This review will explore the current research landscape with respect to HMLs, including compositional considerations and impact on the early life gut microbiota. Recent papers in this field will also be discussed, including a final perspective on current knowledge gaps and potential next research steps for these important but understudied breast milk components.
Evidence supports associations between human gut microbiome variation and multiple health outcomes and diseases. Despite compelling results from
and
models, few findings have been translated into an ...understanding of modifiable causal relationships. Furthermore, epidemiological studies have been unconvincing in their ability to offer causal evidence due to their observational nature, where confounding by lifestyle and behavioural factors, reverse causation and bias are important limitations. Whilst randomized controlled trials have made steps towards understanding the causal role played by the gut microbiome in disease, they are expensive and time-consuming. This evidence that has not been translated between model systems impedes opportunities for harnessing the gut microbiome for improving population health. Therefore, there is a need for alternative approaches to interrogate causality in the context of gut microbiome research. The integration of human genetics within population health sciences have proved successful in facilitating improved causal inference (e.g., with Mendelian randomization MR studies) and characterising inherited disease susceptibility. MR is an established method that employs human genetic variation as natural "proxies" for clinically relevant (and ideally modifiable) traits to improve causality in observational associations between those traits and health outcomes. Here, we focus and discuss the utility of MR within the context of human gut microbiome research, review studies that have used this method and consider the strengths, limitations and challenges facing this research. Specifically, we highlight the requirements for careful examination and interpretation of derived causal estimates and host (i.e., human) genetic effects themselves, triangulation across multiple study designs and inter-disciplinary collaborations. Meeting these requirements will help support or challenge causality of the role played by the gut microbiome on human health to develop new, targeted therapies to alleviate disease symptoms to ultimately improve lives and promote good health.
Fungi and the mycobiome are a fundamental part of the human microbiome that contributes to human health and development. Despite this, relatively little is known about the mycobiome of the preterm ...infant gut. Here, we have characterised faecal fungal communities present in 11 premature infants born with differing degrees of prematurity and mapped how the mycobiome develops during early infancy. Using an ITS1 sequencing-based approach, the preterm infant gut mycobiome was found to be often dominated by a single species, typically a yeast.
was the most abundant genus, with the pathobionts
and
highly prevalent and persistent in these infants. Gestational maturity at birth affected the distribution and abundance of these
, with hospital-associated
more prevalent and abundant in infants born at less than 31 weeks. Fungal diversity was lowest at 6 months, but increased with age and change of diet, with food-associated
most abundant in infants post weaning. This study provides a first insight into the fungal communities present within the preterm infant gut, identifying distinctive features including the prominence of pathobiont species, and the influence age and environmental factors play in shaping the development of the mycobiome.
The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of ...intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS‐induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota‐epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation.
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