Ulcerative colitis is an inflammatory bowel disease with long-term inflammation and an imbalance in the intestinal flora. Long-term disease can lead to an increased risk of colorectal cancer. However, current therapies face problems such as poor efficacy or high side effects.
In order to solve this problem, the Key Laboratory of Biodrug Preparation and Delivery of the Institute of Process Engineering of the Chinese Academy of Sciences (hereinafter referred to as the Institute of Process Engineering) has designed and created an engineered probiotic preparation with chimeric selenium dots based on data mining and clinical findings, and has achieved safe and efficient treatment of ulcerative colitis in a variety of mouse and cynomolgus monkey models by synergistically restoring intestinal microbiota homeostasis and redox homeostasis. The results were published in the international academic journal Cell-Host and Microbe.
01
Data-driven, engineered probiotic manufacturing
▲Probiotics dressed in "magic robes" reach the intestinal inflammation site to perform "magic"
Some studies have found that the imbalance of microflora may exacerbate the intestinal inflammatory response, and supplementation with probiotics can alleviate the symptoms of ulcerative colitis and help restore the balance of the intestinal microbiota.
However, patients with ulcerative colitis have an imbalance in their intestinal flora, so how to find probiotics suitable for their oral administration among the many missing bacteria?
Researchers at the Institute of Process Engineering called on "smart helpers" to digitize the missing bacterial information and use logistic regression algorithms in machine learning to rank the importance of the bacteria, so as to reasonably screen Lactobacillus for oral supplementation.
The pathological microenvironment of colon lesions is complex, and there are many other pathogenic factors. In addition to screening suitable oral probiotics, the researchers found that the elevation of oxidative stress at the lesion site covered all cell types based on bioinformatics analysis, and further clinical samples collected confirmed the above results, and finally found a clear correlation between Lactobacillus abundance, reactive oxygen species (ROS) levels, and inflammation severity.
02
"Two-pronged" synergistic treatment
The discovery of the "smart helper" made researchers realize that the treatment of ulcerative colitis needs to consider both active lactobacillus supplementation at the lesion site and efficient ROS clearance.
Therefore, researchers proposed a strategy for co-delivery of Lactobacillus casei and highly active selenium. First, the formation of a pericellular film was induced on Lactobacillus casei (Lac), and the blue bacteria were dressed in a yellow "magic robe", and the red dots embedded on the "magic robe" represented the ultra-small selenium dots (Se-fLac) that were successfully chimeed on the surface of the bacteria.
▲Schematic diagram of the preparation, enhanced oral delivery, and synergistic homeostatic recovery of Se-fLac
After oral administration, the "magic robe" inlaid with small red dots helps Lactobacillus casei strengthen gastric acid tolerance and intestinal adhesion, allowing them to overcome the adverse environment to reach the intestinal lesion site, efficiently remove ROS, regulate the imbalanced intestinal flora, and achieve the restoration of intestinal redox homeostasis and microflora homeostasis. Moreover, these two aspects reinforce each other to achieve the effect of enhancing the treatment.
03
Excellent efficacy in a variety of disease models
In view of the complexity of the incidence of clinical ulcerative colitis, researchers have constructed a variety of mouse models, and proved that probiotics wearing "magic robes" can significantly improve the symptoms of ulcerative colitis through multiple dimensions such as colon length, proportion of inflammatory cells, and level of inflammatory factors, and the treatment effect is better than that of clinical drugs such as aminosalicylic acid and dexamethasone.
▲Therapeutic effect of Se-fLac in a model of ulcerative colitis in cynomolgus monkeys
In addition, the researchers have built a more clinically friendly model of cynomolgus monkeys. Through treatment, cynomolgus monkeys regained intestinal redox homeostasis and microbiota homeostasis, and the level of inflammation, intestinal lumen bleeding and intestinal wall thickening were significantly improved.
In the future, researchers will integrate artificial intelligence, synthetic biology and other technologies to achieve intelligent construction, efficient delivery and precision treatment of engineered probiotics, and explore their potential for intervention in intestinal aging and intestinal tumor evolution, and cooperate with clinical clinics to promote further translational research. Source: Institute of Process Engineering, Chinese Academy of Sciences Editor-in-charge: Song Tongzhou