Maintenance of sulfomucin is a key end point in the treatment of diarrhea and inflammatory bowel disease (IBD). However, the mechanism underlying the microbial sense to sulfomucin are poorly understood, and to date, there are no therapies targeting the secretion and maturation of sulfomucin in IBD. Considering the important role of gut microbiota in host immune regulation, maintain sulfomucin by modulating the gut microbiota is inspired.
However, due to poor colonization ability and short survival time in the host, the application of probiotics met with substantial challenges. The key to improve probiotic efficiency and colonization is to facilitate the formation of their specific biofilms. Biofilms can achieve the dual function of acting as an adhesive and preventing penetration, helping bacteria defend against external threats. Considering that most Lactobacillus are difficult to form biofilm, there is an urgent need for a material that can serve as a substrate to provide a favorable niche for biofilm formation. Efficient substrate material to support the formation of probiotic biofilms need to meet two essential requirements. Not only should it adhere stably to the inner surface of the gut to provide a stable interface, but it should not hinder the growth of probiotics.
As a tissue engineering scaffold, poly-β-hydroxybutyrate (PHB) may serve as a promising candidate. PHB, the polymer of β-hydroxybutyrate (β-HB), is an important energy substrate of many bacteria. PHB is synthesized when carbon sources are sufficient and other nutrients, like phosphate and nitrogen, are limited, so PHB can assist bacteria survive from nutrient deficiencies and environmental stress. Given this, it may be a prebiotic candidate to resist on disease stress by improving the cell vitality of gut bacteria. Meanwhile, PHB has been reported to improve growth performance and intestinal microbiota richness in some aquatic livestock.
Ning Ma together with lab director Xi Ma, sought to determine whether PHB can improve gut function, optimize microbiota composition, and serve as a favorable niche for probiotic biofilm formation. It will expand new uses for this promising medical implant material. Therefore, with the help of Prof Guo-Qiang Chen from Tsinghua University and Dr. Jingyu Chen, they successfully biosynthesized PHB and found that PHB could alleviate inflammation caused by diarrhea and colitis by enhancing the differentiation of sulfomucin. Microbiota transplantation and clearance together demonstrate that PHB alleviates colitis by enhancing sulfomucin secretion and maturation in a L. johnsonii-dependent manner. Further studies revealed that PHB provides a favorable niche for L. johnsonii biofilm formation to resist disturbance and support its growth. L. johnsonii-biofilm alleviate colitis by regulating fucose residues to promote goblet cell differentiation and subsequent sulfomucin maturation. Importantly, PHB represents a class of guardians, acting as a safe probiotic-biofilm delivery system that significantly promotes probiotic proliferation.
Defa Li, Academician of Chinese Academy of Engineering, commented that, this is a valuable research. It adds weight to the possible role of probiotics and functional materials in the treatment of intestinal inflammation. The application of PHB and biofilm self-coating L. johnsonii carries high translational potential and may be of clinical relevance.
This study is led by Dr. Ning Ma and Pingting Guo (State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University) and Dr. Jingyu Chen (Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University). Prof Xi Ma (State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University) and Prof Guo-Qiang Chen (Center for Synthetic and Systems Biology, MOE Key Lab for Industrial Biocatalysis, School of Life Sciences and Dept Chemical Engineering, Tsinghua University) conceived and designed the study.
Ma, N., et al. (2022) Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin. Science China Life Sciences. doi.org/10.1007/s11427-022-2213-6.