Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study.

BACKGROUND AND AIMS: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming. IMPACT: Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.

Light and carbon: Synthetic biology toward new cyanobacteria-based living biomaterials.

Cyanobacteria are ideal candidates to use in developing carbon neutral and carbon negative technologies; they are efficient photosynthesizers and amenable to genetic manipulation. Over the past two decades, researchers have demonstrated that cyanobacteria can make sustainable, useful biomaterials, many of which are engineered living materials. However, we are only beginning to see such technologies applied at an industrial scale. In this review, we explore the ways in which synthetic biology tools enable the development of cyanobacteria-based biomaterials. First we give an overview of the ecological and biogeochemical importance of cyanobacteria and the work that has been done using cyanobacteria to create biomaterials so far. This is followed by a discussion of commonly used cyanobacteria strains and synthetic biology tools that exist to engineer cyanobacteria. Then, three case studies-bioconcrete, biocomposites, and biophotovoltaics-are explored as potential applications of synthetic biology in cyanobacteria-based materials. Finally, challenges and future directions of cyanobacterial biomaterials are discussed.