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Past Events·

Monday, December 20, 2021

MVIF.4 | 8 & 9 December 2021

with Keynote talk by Prof. Jonathan Eisen


Jonathan Eisen is a Professor at the University of California, Davis with appointments in the Genome Center, the Dept. of Evolution and Ecology, and the Dept. of Medical Microbiology and Immunology. His current research focuses on the evolution, ecology and function of communities of microbes and how the microbes interact with each other and with hosts. Most of his work involves the use of high-throughput DNA sequencing methods to characterize microbes and the use and development of computational methods to analyze this type of data.

Prior to moving to UC Davis Dr. Eisen was on the faculty of The Institute for Genomic Research (TIGR) and held an Adjunct appointment at the Johns Hopkins University. He earned his PhD in Biological Sciences from Stanford University, and his AB in Biology from Harvard College. Dr. Eisen was elected to the American Academy of Microbiology in 2012.


Widespread within-person adaptation in the human gut microbiome

Gut microbiota plays an essential role in regulating human health. How host environment drives microbial evolution was studied in some bacterial species, however, some studies concluded long-term purifying selection while others demonstrated evidence of adaptation. To address this problem, we broadly investigated the within-person evolution of 64 gut commensal species in healthy subjects. We found that most (24 of 27) species with sufficient genetic variation underwent recent adaptation, evidenced by parallel evolution (PE). This finding was supported by three lines of evidence on PE mutations (significantly more than expected, significantly higher dN/dS, significant enrichment of truncations). Moreover, signal transduction pathways underwent the strongest and most widespread positive selection. One striking example is an HTH-type transcriptional regulator (msmR) regulating carbohydrate transportation that underwent widespread PE in six species across 28 people, potentially driven by host diet changes. We resolved the previous debate of gut microbiota evolution showing widespread within-host adaptation, and identified adaptive mutations to guide precise microbiome manipulations.

Anni Zhang

Massachusetts Institute of Technology

Persistent Changes in the Gut Microbiome of COVID-19 Survivors

There are hundreds of millions of survivors of coronavirus disease 2019 (COVID-19), and this group continues to grow. Sars-CoV-2, the causative agent of COVID-19, is detectable in gastrointestinal secretions with measurable impact on the gut microbiome. Given reports that COVID-19 causes persistent symptoms in a majority of COVID survivors, we sought to understand the long-term effects of COVID-19 on the gut microbiome. We longitudinally sampled 18 individuals (n = 14 COVID positive and n = 4 COVID-19 negative household contacts) living in San Francisco. Consistent with prior reports, we detect an association between COVID-19 and the gut microbiome. COVID-19 survivors exhibited greater dispersion of the microbial community. COVID-19 survivors gut microbial communities were more self-distinct when compared to COVID-19 negative individuals. Population level social distancing practices varied during the time of sample collection in our cohort, and we found an unexpected association between population level social distancing and gut microbial community variation. Alpha diversity varied overtime in COVID-19 negative individuals. In contrast alpha diversity over time mirrored the effects observed in beta-dispersion in this group in COVID-19 positive individuals. We analyzed a separate cohort of healthy San Franciscans pre-pandemic where we observed similar variation in alpha diversity over time. We conclude that COVID-19 survivors exhibit greater dispersion of their microbial communities, which is a perturbation observable months after infection and potentially compounded by population level social distancing practices.

Vaibhav Upadhyay

University of California San Francisco

Short- and long-read metagenomics of South African gut microbiomes reveal a transitional composition and novel taxa

While human gut microbiome research has largely focused on western populations, with a small minority of studies investigating nonwestern agriculturalist and hunter-gatherer societies, most of the world’s population resides between these two lifestyle extremes. We present the first study evaluating gut microbiome composition of two transitioning South African populations using short- and long-read sequencing. We analyzed shotgun sequencing samples from adult females living in rural Bushbuckridge (n=117) or urban Soweto (n=51) and find that these microbiomes are intermediate between those of western populations and previously studied agriculturalist and hunter-gatherer African populations. We found that widely used reference collections are incomplete for nonwestern microbiomes, resulting in a larger portion of unclassified sequencing in transitional and nonwestern populations and within-cohort beta diversity patterns that are reversed compared to reference-agnostic sequence comparison patterns. To improve reference databases, we performed de novo metagenomic assembly of long-read sequencing data to generate complete genomes of undescribed taxa, including Treponema and Lentisphaerae species. Collectively, our results suggest that South Africa’s transitional lifestyle and epidemiological conditions are reflected in gut microbiota compositions, and that these populations contain microbial diversity that remains to be described. This work underscores the critical need to broaden the scope of human gut microbiome research and include understudied, nonwestern populations to improve the relevance and accuracy of microbiome discoveries to broader populations.

Dylan Maghini

Stanford University


Association between delivery mode and the healthy newborn meconium microbiota: a systematic review

Meconium is the newborn’s earliest fecal discharge, representing the intestinal content during in utero life, and was formerly thought to be sterile. Recent hypotheses of how meconium microbiota communities are formed include initial colonization during gestation and further influence by delivery mode and other perinatal factors including maternal health. We examined reports of differentially abundant meconium microbiota and alpha diversity by delivery mode (vaginal versus C-section) for newborns of healthy women. Ten articles met criteria for inclusion, representing 601 vaginal deliveries and 281 C-sections. Reported signatures were standardized using the NCBI taxonomy, and reports of differential alpha diversity were recorded. The only concordance in differential abundance signatures was in the genus Stenotrophomonas, reported in two of 10 studies as overabundant in the meconium of C-section delivery newborns when compared to newborns of vaginal delivery, and Enterococcus, reported in two of 10 studies as less abundant. In conclusion, little consistency is seen in published results on over or under abundance of meconium microbiota by delivery mode. Mode of delivery may play a role in the meconium microbiota; however, low replicability across studies limits conclusions that can be drawn about the contribution of mode of delivery to the infant gut microbiome. Future microbiome studies of low microbial biomass meconium should take extra measures to avoid sample contamination, employ negative controls to assess the effectiveness of these measures, set clearly defined inclusion and exclusion criteria for consistency with previous studies (particularly for antibiotics usage and gestational age), and have larger sample sizes.

Shaimaa Mohammed Elsafoury

CUNY Graduate School of Public Health and Health Policy

Transcription shifts in gut bacteria shared between mothers and infants

A portion of strains in the infant gut microbiomes originate from the maternal gut. In the infant gut these bacteria encounter a new metabolic environment that differs from the adult gut, potentially requiring adjustments in their activities. We used community RNA sequencing data (metatranscriptomes) from ten mother-infant dyads participating in the NiPPeR Study to characterize bacterial gene expression shifts following mother-to-infant transmission. Maternally-derived bacterial strains exhibited large scale gene expression shifts following the transmission to the infant gut, with 12,564 activated and 14,844 deactivated gene families. The implicated genes were most numerous and the magnitude shifts greatest in Bacteroides spp. and included genes involved in, for example, carbohydrate utilisation and lysogenic phage activity. Community functions were contrastingly different between mothers and infants on DNA, but not on RNA level; this suggests that bacteria compensated for variations in DNA gene abundance by collectively adjusting gene expression to maintain diverse and stable community activity profiles. Collectively, these data demonstrate environment-dependent, strain-specific shifts in gut bacteria function and underscores the importance of metatranscriptomic analysis in microbiome studies.

Tommi Vatanen

University of Auckland

Genetic Diversity of the Chlorhexidine Resistance in Cultivable Bacteria Isolated from a Medical Intensive Care Unit Environment

The emergence of resistance to biocides is a critical concern in healthcare settings, severely limiting our ability to prevent infection. Chlorhexidine is one of the most widely used disinfectants in the medical intensive care units (MICU) since the 1950s . It is usually applied onto the skin of the patients and health care providers and acts against a wide range of bacteria by disrupting the cell membrane of the bacterial cell wall. However, studies have shown that the exposure to sub-lethal chlorhexidine concentrations may enhance resistance in species well known for emerging antibiotic resistance . To understand the genomic diversity of chlorhexidine tolerance in a high-priority environment, we surveyed an MICU for cultivable organisms demonstrating chlorhexidine resistance and performed whole genome sequencing on selected isolates. We collected 219 swab samples from different locations (e.g. nurse calls, keyboards, bed rails, etc) over two sampling events. The samples were then subjected to cultivation, morphological characterization and selective media screening, resulting in 1415 isolates, of which 308 isolates (21.8%) were able to grow on agar containing 18.75 µg/mL chlorhexidine digluconate. We take a comparative genomics approach to identifying genes related to chlorhexidine resistance by comparing genomes of the same species with different chlorhexidine susceptibility. Future work will focus on testing cross-resistance between chlorhexidine and clinically relevant antibiotics in the collected isolates. As the hospital microbiome can serve as a source of antibiotic-resistant bacteria, contributing to hospital-acquired infections, the genetic characterization of chlorhexidine-resistant organisms at environmental locations within the MICU has important implications for disinfection and patient safety, as well as advancing our basic understanding of resistance to this widely used disinfectant.

Yuhan Weng

Northwestern University