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Wednesday, June 28, 2023

MVIF.20 June23 Ami Bhatt

MVIF.20 June23 Ami Bhatt

MVIF.20 June23 Ami Bhatt

Prof. Ami Bhatt’s Bio

Prof. Ami Bhatt is an Associate Professor of Medicine and Genetics at Stanford University. She received her MD and PhD in Biochemistry and Molecular Biology at the University of California, San Francisco, and received the Fineberg Award for Excellence in Teaching. She carried out her post-doctoral studies at the Broad Institute of Harvard and MIT, as well as her residency and chief residency in Internal Medicine at Brigham and Women's Hospital, and she has been a fellow in Hematology and Oncology at the Dana-Farber Cancer Institute in Boston.

Prof. Bhatt's lab seeks to improve outcomes in patients with haematological malignancies by studying the dynamics of the microbiome in immunocompromised individuals, also through the use of cutting-edge computational technologies to tackle the complexity of microbial genomics.

Prof. Bhatt is also committed to improving cancer care, education and research in resource-limited settings. She is a co-founder and co-president of the non-profit organisation Global Oncology, the Director of Global Oncology for the Center for Innovation in Global Health at Stanford University, and she has served as a visiting lecturer at the Tokyo Medical and Dental University, Trinity College in Dublin, Ireland and the University of Botswana.

Selected Talks

Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome

Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci harboring variants associated with milk cell gene expression unique to the lactating mammary gland. Genetic effects on milk gene expression included genes with roles in the biosynthesis of specific human milk oligosaccharides (HMO), including a genetic variant that increases the expression of the gene GCNT3 in milk and is also associated with increased concentration of the HMO FLNH. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance of Bifidobacteria in the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.

Link to OA paper:

Kelsey Johnson
University of Minnesota

Feeding method is the key factor characterizing the composition and functional profiles of the 6-month infant gut microbiome

The infant gut microbiome begins development at birth, with major transition points occurring around the commencement of breastfeeding, the introduction of solid foods, and the cessation of breastfeeding. Until around three years of age, the development of the infant gut microbiome remains highly plastic and easily influenced by environmental factors. Developing a diverse and rich gut microbiome during this sensitive period is crucial to setting up a stable gut microbiome into adulthood, and to prevent gut dysbiosis. We have characterised the overall composition and functional profiles of the 6-month old gut microbiome using whole genome shotgun metagenomics sequencing and identified the key influencing environmental factors. Specifically, we discuss the effect of timing of solid food introduction, and feeding method on diversity. We also identified the differences in colonising species between breastfed and bottle-fed infants. We found the 6-month gut microbiome to be characterised by high rates of inter-individual variation. We also found infants fed exclusively formula milk had a higher overall diversity than infants fed a breastmilk diet and breastfed infants had a higher abundance of Bifidobacterium spp. We also did not identify any significantly different metabolic pathways between different environmental factors.

Kimberley Parkin
Telethon Kids Institute, Perth, Australia

Steamed broccoli sprouts alleviate gut inflammation and retain gut microbiota against DSS-induced dysbiosis

Inflammatory Bowel Diseases (IBD) are devastating conditions of the gastrointestinal tract with limited treatments, and dietary intervention may be effective, affordable, and safe for managing symptoms. Ongoing research has identified inactive compounds in broccoli sprouts, like glucoraphanin, and that mammalian gut microbiota play a role in metabolizing it to the anti-inflammatory sulforaphane. The objectives were to identify biogeographic location of participating microbiota and correlate that to health outcomes. We fed specific pathogen free C57BL/6 mice either a control diet or a 10% steamed broccoli sprout diet, and gave a three-cycle regimen of 2.5% dextran sodium sulfate (DSS) in drinking water over a 40-day experiment to simulate chronic, relapsing ulcerative colitis. We monitored body weight, fecal characteristics, fecal lipocalin, and sequenced bacterial communities from the contents and mucosa in the jejunum, cecum, and colon. Mice fed the broccoli sprout diet while receiving DSS performed better than mice fed the control diet while receiving DSS for all disease parameters, including significantly more weight gain (2-way ANOVA, p < 0.05), lower Disease Activity Index scores (2-way ANOVA, p < 0.001), and higher bacterial richness in all gut locations (linear regression model, p < 0.01 for all locations measured). Bacterial communities were assorted by gut location except in the mice receiving the control diet and DSS treatment (Beta-diversity, ANOVA, p < 0.05 for each). Importantly, our results suggested that broccoli sprout feeding completely abrogated the effects of DSS on gut microbiota, as bacterial communities were similar between mice receiving broccoli sprouts with and without DSS. Spatially resolved microbial communities provide greater insight when investigating host-microbe interactions. Here, we show that a 10% broccoli sprout diet protects mice from the negative effects of dextran sodium sulfate induced colitis, that colitis erases biogeographical patterns of bacterial communities in the gut, and that the cecum is not likely to be a significant contributor to colonic bacteria of interest in the DSS mouse model of ulcerative colitis.

Link to OA paper:

Johanna M Holman

University of Maine

Fusobacterium nucleatum subspecies exhibit oral niche-specific biases

Fusobacterium nucleatum, a ubiquitous member of the human oral and gut microbiomes, is strongly associated with the development of multiple human diseases including periodontitis, oral/extraoral abscesses, and several types of cancer. F. nucleatum is currently divided into four subspecies: F. nucleatum subspecies nucleatum (Fn. nucleatum), animalis (Fn. animalis), polymorphum (Fn. polymorphum), and vincentii/fusiforme (Fn. vincentii). Although these subspecies have been historically considered as functionally interchangeable, recent clinical studies of colorectal tumor-associated F. nucleatum have suggested this perception may be inaccurate. Consequently, we aimed to determine whether F. nucleatum subspecies prevalence in the oral cavity correlates with oral health status. Patient-matched specimens of dental plaque and odontogenic abscess were analyzed with both culture-independent and culture-dependent approaches using 58 and 44 paired samples, respectively. Pangenome, phylogenetic and functional enrichment analysis of Fusobacterium species and F. nucleatum subspecies were conducted using the Anvi’o workflow. Both culture-independent and -dependent analyses similarly revealed a highly biased distribution of F. nucleatum subspecies in the oral cavity, with most patients harboring multiple subspecies. In dental plaque, Fn. polymorphum is the dominant organism, whereas Fn. animalis is particularly prevalent within abscesses. Surprisingly, the most heavily studied subspecies, Fn. nucleatum, was only a minor constituent within the entire specimen collection. In agreement with the clinical data, phylogenetic and comparative genomic analyses identified substantial distinctions among F. nucleatum subspecies. The heterogeneous distribution of F. nucleatum subspecies within oral plaque and abscess specimens reveals niche-specific preferences, with Fn. animalis likely exhibiting the greatest pathogenic potential. Both the clinical and genomic data strongly suggest that each F. nucleatum subspecies likely comprises unique Fusobacterium species.

Madeline Krieger

Oregon Health and Science University