Background
In the contemporary world, chronic diseases such as hypertension, diabetes, and colitis are progressively emerging as significant global health threats. According to the World Health Organization (WHO), the prevalence of hypertension has already surpassed 1.28 billion individuals. The latest research published in The Lancet reveals that the number of people affected by diabetes has already exceeded 529 million in 2021 and is projected to surpass 1.3 billion by 2050. Simultaneously, another article published in The Lancet highlights that by 2023, an estimated five million cases of colitis will be reported worldwide with a rising global incidence rate. These figures are not just cold statistics, they represent a fresh life behind them, and the health challenges they face. The escalating occurrence of these ailments imposes a substantial burden on patients and their families while also exerting a profound impact on socio-economic aspects.
The occurrence of diabetes
The occurrence of diabetes is primarily classified into type 1 and type 2 diabetes.
Type 1 diabetes, typically observed in young individuals, is an autoimmune disease characterized by insufficient insulin secretion. Insulin, secreted by pancreatic beta cells, plays a crucial role in lowering blood sugar levels and promoting glycogen synthesis within our body. Inadequate insulin secretion hinders the prompt conversion of glucose into glycogen after a rise in blood sugar levels, impeding the uptake of glucose by cellular tissues and ultimately leading to the development of diabetes.
Conversely, type 2 diabetes predominantly arises from insulin resistance within the body. For effective promotion of cellular glucose uptake, insulin needs to bind with receptors on cells akin to a key opening a door for glucose entry. Failure of our body's cells to recognize insulin results in insulin resistance where the cellular "door" remains closed, preventing glucose from entering cells while causing its accumulation in the bloodstream and subsequent elevation of blood sugar levels.
The occurrence of Hypertension
Hypertension is primarily caused by increased vasoconstriction, which can be likened to the restricted flow of water through pipes. Lifestyle and dietary habits play pivotal roles in the development of hypertension. Excessive body weight places additional strain on the heart, necessitating heightened pumping efforts and subsequently elevating blood pressure; insufficient physical activity diminishes vascular elasticity and impedes blood circulation; smoking induces vasoconstriction and damages vessel walls, further exacerbating high blood pressure; excessive alcohol consumption stimulates the nervous system, resulting in elevated blood pressure; moreover, heightened levels of stress and anxiety in modern life can trigger an augmented release of stress hormones that promote vasoconstriction and accelerate heart rate, thereby raising blood pressure. Unhealthy lifestyle choices and dietary habits not only contribute to hypertension but may also predispose individuals to other health issues such as diabetes. A diet rich in sodium, saturated fats, cholesterol-laden foods coupled with a dearth of fruits and vegetables all heighten the risk of developing hypertension.
Current Strategies
Conventional diabetes treatment
Oral hypoglycemic drugs are the primary therapeutic approach for diabetes, and they exert their blood sugar-lowering effects through diverse mechanisms. Certain medications stimulate insulin secretion, while others mitigate insulin resistance or inhibit hepatic glucose production to achieve the desired glycemic control. Insulin injections directly supplement endogenous insulin requirements, facilitating glucose uptake and thereby reducing blood sugar levels. Insulin injections are frequently combined with dietary management and physical activity to facilitate weight control and enhance insulin sensitivity.
Conventional hypertension treatment
The primary treatment options for hypertension encompass lifestyle modifications and pharmacotherapy. Lifestyle modifications, such as dietary control, increased physical activity, and stress reduction, effectively contribute to blood pressure reduction. Pharmacotherapy commonly involves the administration of diuretics, calcium channel blockers, ACE inhibitors, beta-blockers, among others. These medications function by inhibiting vasoconstriction or reducing cardiac contractility to decrease blood volume and exert antihypertensive effects.
While traditional medications are efficacious in managing diabetes, they may also entail adverse effects and necessitate prolonged usage. Additionally, diabetic patients must routinely monitor their blood glucose levels to avert occurrences of hypoglycemia or hyperglycemia.
Solution
The engineering strain chosen for our project is Zymomonas mobilis, primarily due to its anaerobic fermentation capability and high tolerance towards sugar and acid. This strain exhibits enhanced suitability for the intestinal environment and produces fructooligosaccharides, which can effectively promote the growth of gut microbiota and potentially achieve targeted colonization. By employing targeted metabolic engineering design, modification, testing, and application of Zymomonas mobilis, we aim to develop a synbiotic microbial therapy that integrates prevention, diagnostic reporting, and responsive treatment modules.
Compared to conventional treatment methods, synbiotic therapy offers superior levels of safety, stability, adaptability, and targeting. Moreover, the duration of its medicinal effects is prolonged, effectively addressing the requirement for patients to adhere to specific timing and dosages in traditional treatments.
In contrast, synbiotic therapy provides a more dynamic and intelligent approach to treatment. Through genetic engineering techniques, specific microorganisms can be engineered to automatically respond when blood sugar or blood pressure exceeds normal ranges. Once blood sugar or blood pressure returns to normal levels, these microorganisms activate a suiside mechanism to prevent excessive lowering of glucose or blood pressure. This enhances the safety and effectiveness of treatment while minimizing side effects and monitoring burdens associated with traditional drug therapies. The precision and safety offered by synbiotic therapy make it a potential breakthrough in the treatment of diabetes and hypertension with promising prospects for wider clinical application in the future.
Prospects
The Lasker Awards, considered as the 'litmus test' for Nobel Prizes in the field of biomedical research, were officially announced on September 19, 2024. Among them, the Clinical Medical Research Award was bestowed upon three scientists who made groundbreaking discoveries and advancements in GLP-1-based drug development. They emphasized that with the escalating global prevalence of obesity and diabetes, there is a projected surge in market demand for GLP-1. Furthermore, beyond its application in diabetes treatment, GLP-1 has exhibited promising therapeutic potential across diverse disease domains. This underscores the extensive prospects and untapped possibilities of our project. We firmly believe that through relentless dedication to advancing our project, we will ultimately accomplish our objective of facilitating a healthier and more vibrant state of life for all.
