Succession of Bifidobacterium longum strains in response to the changing early-life nutritional environment reveals specific adaptations to distinct dietary substrates

Diet-microbe interactions play a crucial role in infant development and modulation of the early-life microbiota. The genus Bifidobacterium dominates the breast-fed infant gut, with strains of B. longum subsp. longum (B. longum) and B. longum subsp. infantis (B. infantis) particularly prevalent. Although transition from milk to a more diversified diet later in infancy initiates a shift to a more complex microbiome, specific strains of B. longum may persist in individual hosts for prolonged periods of time. Here, we sought to investigate the adaptation of B. longum to the changing infant diet. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to glycosyl hydrolase families and enzymes, which corresponded to different dietary stages. Complementary phenotypic growth studies indicated strain-specific differences in human milk oligosaccharide and plant carbohydrate utilisation profiles of isolates between and within individual infants, while proteomic profiling identified active polysaccharide utilisation loci involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum subspecies/strain genomic and carbohydrate utilisation diversity, which aligns with a changing nutritional environment: i.e. moving from breast milk to a solid food diet. These data provide additional insights into possible mechanisms responsible for the competitive advantage of this Bifidobacterium species and its long-term persistence in a single host and may contribute to rational development of new dietary therapies for this important developmental window

Succession of Bifidobacterium longum strains in response to a changing early life nutritional environment reveals dietary substrate adaptations

Diet-microbe interactions play a crucial role in modulation of the early life microbiota and infant health. Bifidobacterium dominates the breast-fed infant gut and may persist in individuals during transition from a milk-based to a more diversified diet. Here, we investigated adaptation of B. longum to the changing nutritional environment. Genomic characterisation of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to carbohydrate metabolism, which corresponded to different dietary stages. Complementary phenotypic studies indicated strain-specific differences in utilisation of human milk oligosaccharides and plant carbohydrates, while proteomic profiling identified gene clusters involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum diversity and provide additional insights into possible competitive advantage mechanisms of this Bifidobacterium species and its persistence in a single host

The Role of Demographic and Clinical Characteristics on Risk of COVID-19 Related Infection and Mortality

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) which causes Covid-19, global health systems have struggled to cope with the rising number of related infections, acute admissions and mortalities. Poorer clinical outcomes have been observed amongst older patients with Covid-19 and males, and in those who are obese or who have darker skin(1) . Additionally, poorer outcomes including increased mortality have been associated with low vitamin D status(2,3) . The current observational study aimed to elucidate the association between patient demographic, anthropometric, clinical and biometric characteristics and Covid-19 disease severity and mortality

Synthesis and in vivo evaluation of insulin-loaded whey beads as an oral peptide delivery system

For many diabetics, daily, lifelong insulin injections are required to effectively manage blood glucose levels and the complications associated with the disease. This can be a burden and reduces patient quality of life. Our goal was to develop a more convenient oral delivery system that may be suitable for insulin and other peptides. Insulin was entrapped in 1.5-mm beads made from denatured whey protein isolate (dWPI) using gelation. Beads were then air-dried with fumed silica, Aerosil®. The encapsulation efficiency was ~61% and the insulin loading was ~25 µg/mg. Dissolution in simulated gastric-, and simulated intestinal fluids (SGF, SIF) showed that ~50% of the insulin was released from beads in SGF, followed by an additional ~10% release in SIF. The omission of Aerosil® allowed greater insulin release, suggesting that it formed a barrier on the bead surface. Circular dichroism analysis of bead-released insulin revealed an unaltered secondary structure, and insulin bioactivity was retained in HepG2 cells transfected to assess activation of the endogenous insulin receptors. Insulin-entrapped beads were found to provide partial protection against pancre-atin for at least 60 min. A prototype bead construct was then synthesised using an encapsulator system and tested in vivo using a rat intestinal instillation bioassay. It was found that 50 IU/kg of entrapped insulin reduced plasma glucose levels by 55% in 60 min, similar to that induced by sub-cutaneously (s.c.)-administered insulin (1 IU/kg). The instilled insulin-entrapped beads produced a relative bioavailability of 2.2%. In conclusion, when optimised, dWPI-based beads may have potential as an oral peptide delivery system.Irish Research CouncilAnaBio Technologies LtdInsucaps LtdUCD School of Veterinary Medicin

Social media use, attitudes, behaviours and perceptions of online professionalism amongst dental students

Use of social media has increased amongst health professionals. This has benefits for patient care but also introduces risks for confidentiality and professional fitness to practise. This study aimed to examine dental student attitudes towards professional behaviour on social media. The secondary aim was to establish the extent and nature of social media use and exposure to potentially unprofessional behaviours. A cross-sectional study was carried out in one dental school. Data were collected using questionnaires to examine social media use, perceptions and attitudes towards social media and professional behaviours online. Students who responded (n=155) all used social media at least once per week; most used more than one platform. Students were aware of the relationship between social media use and professional practice. Posting drunken photographs and interacting with staff and patients online were widely considered as unprofessional. Security settings affected behaviour and most had seen inappropriate behaviours online. Students use social media extensively. Students are aware of the risks but there is a greater sense of safety in closed groups and many students are exposed to potentially inappropriate content online. This suggests that there are opportunities to reduce these risks through training to help students manage these risks

A New Look at Familial Risk of Inflammatory Bowel Disease in the Ashkenazi Jewish Population

Background and Aims: The inflammatory bowel diseases (IBD) are particularly common among the Ashkenazi Jewish (AJ) population. Population-specific estimates of familial risk are important for counseling; however, relatively small cohorts of AJ IBD patients have been analyzed for familial risk to date. This study aimed to recruit a new cohort of AJ IBD patients, mainly from the UK, to determine the familial occurrence of disease. / Methods: A total of 864 AJ IBD patients were recruited through advertisements, hospital clinics, and primary care. Participants were interviewed about their Jewish ancestry, disease phenotype, age of diagnosis, and family history of disease. Case notes were reviewed. / Results: The 864 probands comprised 506 sporadic and 358 familial cases, the latter with a total of 625 affected relatives. Of the UK cases, 40% had a positive family history with 25% having at least one affected first-degree relative. These percentages were lower among those recruited through hospital clinics and primary care (33% for all relatives and 22% among first-degree relatives). Examining all probands, the relative risk of IBD for offspring, siblings, and parents was 10.5, 7.4, and 4, respectively. Age of diagnosis was significantly lower in familial versus sporadic patients with Crohn’s disease. / Conclusions: This study reports familial risk estimates for a significant proportion of the AJ IBD population in the UK. The high rate of a positive family history in this cohort may reflect the greater genetic burden for IBD among AJs. These data are of value in predicting the likelihood of future recurrence of IBD in AJ families

Quantitative electron phase imaging with high sensitivity and an unlimited field of view

As it passes through a sample, an electron beam scatters, producing an exit wavefront rich in information. A range of material properties, from electric and magnetic field strengths to specimen thickness, strain maps and mean inner potentials, can be extrapolated from its phase and mapped at the nanoscale. Unfortunately, the phase signal is not straightforward to obtain. It is most commonly measured using off-axis electron holography, but this is experimentally challenging, places constraints on the sample and has a limited field of view. Here we report an alternative method that avoids these limitations and is easily implemented on an unmodified transmission electron microscope (TEM) operating in the familiar selected area diffraction mode. We use ptychography, an imaging technique popular amongst the X-ray microscopy community; recent advances in reconstruction algorithms now reveal its potential as a tool for highly sensitive, quantitative electron phase imaging

Comparative in situ analyses of cell wall matrix polysaccharide dynamics in developing rice and wheat grain

Cell wall polysaccharides of wheat and rice endosperm are an important source of dietary fibre. Monoclonal antibodies specific to cell wall polysaccharides were used to determine polysaccharide dynamics during the development of both wheat and rice grain. Wheat and rice grain present near synchronous developmental processes and significantly different endosperm cell wall compositions, allowing the localisation of these polysaccharides to be related to developmental changes. Arabinoxylan (AX) and mixed-linkage glucan (MLG) have analogous cellular locations in both species, with deposition of AX and MLG coinciding with the start of grain filling. A glucuronoxylan (GUX) epitope was detected in rice, but not wheat endosperm cell walls. Callose has been reported to be associated with the formation of cell wall outgrowths during endosperm cellularisation and xyloglucan is here shown to be a component of these anticlinal extensions, occurring transiently in both species. Pectic homogalacturonan (HG) was abundant in cell walls of maternal tissues of wheat and rice grain, but only detected in endosperm cell walls of rice in an unesterified HG form. A rhamnogalacturonan-I (RG-I) backbone epitope was observed to be temporally regulated in both species, detected in endosperm cell walls from 12 DAA in rice and 20 DAA in wheat grain. Detection of the LM5 galactan epitope showed a clear distinction between wheat and rice, being detected at the earliest stages of development in rice endosperm cell walls, but not detected in wheat endosperm cell walls, only in maternal tissues. In contrast, the LM6 arabinan epitope was detected in both species around 8 DAA and was transient in wheat grain, but persisted in rice until maturity

Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis

BACKGROUND: Bacterial vaginosis (BV) is a polymicrobial syndrome characterized by a change in vaginal flora away from predominantly Lactobacillus species. The cause of BV is unknown, but the condition has been implicated in diverse medical outcomes. The bacterium Atopobium vaginae has been recognized only recently. It is not readily identified by commercial diagnostic kits. Its clinical significance is unknown but it has recently been isolated from a tuboovarian abcess. METHODS: Nucleotide sequencing of PCR amplified 16S rRNA gene segments, that were separated into bands within lanes on polyacrylamide gels by denaturing gradient gel electrophoresis (DGGE), was used to examine bacterial vaginal flora in 46 patients clinically described as having normal (Lactobacillus spp. predominant; Nugent score ≤ 3) and abnormal flora (Nugent score ≥ 4). These women ranged in age from 14 to 48 and 82% were African American. RESULTS: The DGGE banding patterns of normal and BV-positive patients were recognizably distinct. Those of normal patients contained 1 to 4 bands that were focused in the centre region of the gel lane, while those of BV positive patients contained bands that were not all focused in the center region of the gel lane. More detailed analysis of patterns revealed that bands identified as Atopobium vaginae were present in a majority (12/22) of BV positive patients, while corresponding bands were rare (2/24) in normal patients. (P < 0.001) Two A. vaginae isolates were cultivated from two patients whose DGGE analyses indicated the presence of this organism. Two A. vaginae 16S rRNA gene sequences were identified among the clinical isolates. The same two sequences were obtained from DGGE bands of the corresponding vaginal flora. The sequences differed by one nucleotide over the short (~300 bp) segment used for DGGE analysis and migrated to slightly different points in denaturing gradient gels. Both isolates were strict anaerobes and highly metronidazole resistant. CONCLUSION: The results suggest that A. vaginae may be an important component of the complex bacterial ecology that constitutes abnormal vaginal flora. This organism could play a role in treatment failure if further studies confirm it is consistently metronidozole resistant