The Gut Microbiota Composition in Dichorionic Triplet Sets Suggests a Role for Host Genetic Factors

peer-reviewedMonozygotic and dizygotic twin studies investigating the relative roles of host genetics and environmental factors in shaping gut microbiota composition have produced conflicting results. In this study, we investigated the gut microbiota composition of a healthy dichorionic triplet set. The dichorionic triplet set contained a pair of monozygotic twins and a fraternal sibling, with similar pre- and post-natal environmental conditions including feeding regime. V4 16S rRNA and rpoB amplicon pyrosequencing was employed to investigate microbiota composition, and the species and strain diversity of the culturable bifidobacterial population was also examined. At month 1, the monozygotic pair shared a similar microbiota distinct to the fraternal sibling. By month 12 however, the profile was more uniform between the three infants. Principal coordinate analysis (PCoA) of the microbiota composition revealed strong clustering of the monozygotic pair at month 1 and a separation of the fraternal infant. At months 2 and 3 the phylogenetic distance between the monozygotic pair and the fraternal sibling has greatly reduced and by month 12 the monozygotic pair no longer clustered separately from the fraternal infant. Pulse field gel electrophoresis (PFGE) analysis of the bifidobacterial population revealed a lack of strain diversity, with identical strains identified in all three infants at month 1 and 12. The microbiota of two antibiotic-treated dichorionic triplet sets was also investigated. Not surprisingly, in both triplet sets early life antibiotic administration appeared to be a major determinant of microbiota composition at month 1, irrespective of zygosity. By month 12, early antibiotic administration appeared to no longer exert such a strong influence on gut microbiota composition. We hypothesize that initially host genetics play a significant role in the composition of an individual’s gut microbiota, unless an antibiotic intervention is given, but by month 12 environmental factors are the major determinant.This study was performed as part of the INFANTMET project (10/RD/Infantmet/MFRC/705) and was funded by the Government of Ireland's Department of Agriculture Fisheries and in part by Alimentary Pharmabiotic Centre. KM is a Teagasc Walsh Fellow. CS, RPR and PWOT are members of The Alimentary Pharmabiotic Centre, which is a Centre for Science and Technology (CSET) funded by the Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (Grant no. 02/CE/B124 and 07/CE/B1368)

The Composition of Human Milk and Infant Faecal Microbiota Over the First Three Months of Life: A Pilot Study

peer-reviewedHuman milk contains a diverse array of bioactives and is also a source of bacteria for the developing infant gut. The aim of this study was to characterize the bacterial communities in human milk and infant faeces over the first 3 months of life, in 10 mother-infant pairs. The presence of viable Bifidobacterium and Lactobacillus in human milk was also evaluated. MiSeq sequencing revealed a large diversity of the human milk microbiota, identifying over 207 bacterial genera in milk samples. The phyla Proteobacteria and Firmicutes and the genera Pseudomonas, Staphylococcus and Streptococcus were the predominant bacterial groups. A core of 12 genera represented 81% of the microbiota relative abundance in milk samples at week 1, 3 and 6, decreasing to 73% at week 12. Genera shared between infant faeces and human milk samples accounted for 70–88% of the total relative abundance in infant faecal samples, supporting the hypothesis of vertical transfer of bacteria from milk to the infant gut. In addition, identical strains of Bifidobacterium breve and Lactobacillus plantarum were isolated from the milk and faeces of one mother-infant pair. Vertical transfer of bacteria via breastfeeding may contribute to the initial establishment of the microbiota in the developing infant intestine

Thinking Globally in the Pursuit of Individual Identity: Diversity, Equity, and Inclusion in the International Journal of Medical Students (IJMS)

Diversity, equity, and inclusion (DEI) are core values that are unequivocally essential to healthcare research and practice. However, global health inequities remain pervasive and disruptive to the delivery of healthcare. This unacceptable lack of inclusivity and equity infiltrates all aspects of medicine, including research and publication. Accordingly, there is a dissemination of unbalanced and homogenous perspectives which are not representative of the global population. The International Journal of Medical Students (IJMS) has strived to counter such biases through the development of content and the process of its publication. Further, the selection of its editorial team and ambassadors is conducted with the intention of diversity. We respect individual differences and celebrate them as strengths adding to the quality of our journal. Therefore, the IJMS has taken a positive step toward an equitable environment by publishing a policy statement on DEI. We hope to lead by example by fostering a culture of inclusivity for all researchers, regardless of background. Though, we recognize the complexity of implementing comprehensive DEI practices and consider it our duty to the community that we continuously develop through a dedicated effort and iterative process

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice

peer-reviewedBackground Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS. Results Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters. Conclusions In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women

Medical Student Research Journals: The International Journal of Medical Students (IJMS) Legacy

The International Journal of Medical Students (IJMS) has emerged over the past decade as a critical platform for showcasing medical student innovation and experiences. Though the work of trainees has historically been undervalued and over scrutinized, the IJMS is committed to highlighting the immense capacity for novel and robust research in this cohort. Thus, supporting an upcoming generation of leaders in medicine and academia to gain confidence in their work and contribute positively to the scientific community. In this issue of the IJMS, we are proud to present 16 articles from the Americas, Europe, Asia, and Africa. Original research articles cover a breadth of topics, including medical training, impacts of the COVID-19 pandemic on teaching and communication, pediatric respiratory illness, gender equity in medicine, understudied illnesses, and cardiovascular disease. The IJMS is proud to feature first-hand experiences of medical trainees in each issue. Accordingly, in the present issue perspectives of six medical students are outlined following unique and career-altering experiences. From working in palliative care to international outreach program, local vaccination initiatives, and the creation of a student-oriented research and innovation council in India. The IJMs extends our gratitude to our contributors, team, and readers for another remarkable issue

TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.

HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion

Draft genome sequence of Bacillus thuringiensis DPC6431, producer of the bacteriocin thuricin CD

We report the draft genome sequence of Bacillus thuringiensis DPC6431, a producer of the anticlostridial bacteriocin thuricin CD and isolated from a human fecal sample. The assembly comprises 96 contigs for a total of 5,581,839 bp, with 32.5% G+C content

Deficiency of essential dietary n-3 PUFA disrupts the caecal microbiome and metabolome in mice

peer-reviewedn-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes