Biology subjects

Chen-Liaw, A.

Publications and source records attributed to Chen-Liaw, A..

4 recordsLinked to original sources

bioRxiv2025

Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein

We examine disease-specific and cross-disease functions of the human gut microbiome by colonizing germ-free mice, at risk for inflammatory arthritis, colitis, or neuroinflammation, with over 100 human fecal microbiomes from subjects with rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, ulcerative colitis, Crohns disease, or colorectal cancer. We find common inflammatory phenotypes driven by microbiomes from individuals with intestinal inflammation or inflammatory arthritis, as well as distinct functions specific to microbiomes from multiple sclerosis patients. Inflammatory disease in mice colonized with human microbiomes correlated with systemic inflammation, measured by C-reactive protein, in the human donors. These cross-disease patterns of human microbiome pathogenicity mirror features of the inflammatory diseases, including therapeutic targets and the presence or absence of systemic inflammation, suggesting shared and disease-specific mechanisms by which the microbiome is shaped and drives pathogenic inflammatory responses.

immunology↗

bioRxiv2022

Gut microbiota bacterial strain richness is species specific and limits therapeutic engraftment

Despite the fundamental role of strain variation in gut microbiota function, the number of unique strains of a species that can stably colonize the human gut is still unknown. In this work, we determine the strain richness of common gut species using thousands of sequenced bacterial isolates and metagenomes. We find that strain richness varies across species, is transferable by fecal microbiota transplantation, and is low in the gut compared to other environments. Therapeutic administration of supraphysiologic numbers of strains per species only temporarily increases recipient strain richness, which subsequently converges back to the population average. These results suggest that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and provide a theoretical framework for strain engraftment and replacement in fecal microbiota transplantation and defined live biotherapeutic products.

microbiology↗

bioRxiv2020

Immunoglobulin A Antibody Composition Is Sculpted to Bind the Self Gut Microbiome

Despite being the most abundantly secreted immunoglobulin isotype, the reactivity of IgA antibodies towards each individuals own gut commensal bacteria still remains elusive. By colonizing germ-free mice with defined commensal bacteria, we found the binding specificity of bulk fecal and serum IgA towards resident gut bacteria resolves well at the species level and has modest strain level specificity. IgA hybridomas generated from lamina propria B cells of gnotobiotic mice showed that most IgA clones recognized a single bacterial species, while a small portion displayed polyreactivity. Species-specific IgAs had a range of strain specificities. Given the unique bacterial species and strain composition in each individuals gut, our findings suggest the IgA repertoire is uniquely shaped to bind our self gut bacteria.

immunology↗

bioRxiv2020

Quantification of discrete gut bacterial strains following fecal transplantation for recurrent Clostridioides difficile infection demonstrates long-term stable engraftment in non-relapsing recipients

Fecal Microbiota Transplantation (FMT), while successful for the treatment of recurrent Clostridioides difficile (rCDI) infection, lacks a quantitative identification of the discrete bacterial strains that transmit and stably engraft in recipients, and their association with clinical outcomes. Using >1,000 unique bacterial strains isolated and sequenced from a combination of 22 FMT donors and recipients, we develop a statistical approach Strainer to detect and track sequenced bacterial strains from low depth metagenomic sequencing data. On application to 14 FMT interventions, we detect stable and high engraftment of [~]71% of gut microbiota strains in recipients at even 5-years post-transplant, a remarkably durable therapeutic from a single administration. We found differential transmission and engraftment efficacy across bacterial taxonomic groups over short and long-time scales. Although [~]80% of the original pre-FMT recipient strains were eliminated by the FMT, those strains that remain persist even 5 years later, along with newer strains acquired from the environment. The precise quantification of donor bacterial strains in recipients independently explained the clinical outcomes of early and late relapse. Our framework identifies the consistently engrafting discrete bacterial strains for use in Live Biotherapeutic Products (LBP) as a safer, scalable alternative to FMT and enables systematic evaluation of different FMT and LBP study designs.

immunology↗