Biology subjects

Morjaria, S.

Publications and source records attributed to Morjaria, S..

3 recordsLinked to original sources

bioRxiv2019

Monocyte reconstitution and gut microbiota composition after hematopoietic stem cell transplantation

BackgroundMonocytes are an essential cellular component of the innate immune system that support the hosts effectivenss to combat a range of infectious pathogens. Hemopoietic cell transplantation (HCT) results in transient monocyte depletion, but the factors that regulate recovery of monocyte populations are not fully understood. In this study, we investigated whether the composition of the gastrointestinal microbiota is associated with the recovery of monocyte homeostasis after HCT.\n\nMethodsWe performed a single-center, prospective, pilot study of 18 recipients of either autologous or allogeneic HCT. Serial blood and stool samples were collected from each patient during their HCT hospitalization. Analysis of the gut microbiota was done using 16S rRNA gene sequencing and flow cytometric analysis was used to characterize the phenotypic composition of monocyte populations.\n\nResultsDynamic fluctuations in monocyte reconstitution occurred after HCT and large differences were observed in monocyte frequency among patients over time. Recovery of absolute monocyte counts and monocyte subsets showed significant variability across the heterogeneous transplant types and conditioning intensities; no relationship to the microbiota composition was observed in this small cohort.\n\nConclusionA relationship between the microbiota composition and monocyte homeostasis could not be firmly established in this pilot study.

immunology↗

bioRxiv2019

The gut microbiota influences circulatory immune cell dynamics in humans

The gut microbiota influences development and homeostasis of the mammalian immune system1-3, can alter immune cell compositions in mice4-7, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells8-12. Still, our understanding of how the microbiota modulates immune cells dynamics remains limited, particularly in humans where a lack of deliberate manipulations makes inference challenging. Here we study hundreds of hospitalized--and closely monitored--patients receiving hematopoietic cell transplantation as they recover from chemotherapy and stem cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously. We analyzed daily changes in white blood cells from 2,235 patients, and 10,680 longitudinal microbiota samples to identify bacteria associated with those changes. Bayesian inference and validation across patient cohorts revealed consistent associations between gut bacteria and white blood cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks. We contrasted the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism to estimate the potential of the microbiota to influence peripheral immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.

microbiology↗

bioRxiv2019

Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation

BackgroundDramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high-resolution through daily stool sampling and assess the impact of individual antibiotics on those changes.\n\nMethodsWe collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multi-parallel 16S rRNA gene sequencing, as well as density of bacteria in stool by qPCR. We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics.\n\nResultsThe greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes.\n\nConclusionsOur approach of daily sampling, bacterial density determination and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.

microbiology↗