Team:BNU-China/Description

What's the Problem?

Obesity is defined as body mass index (BMI) over 30 kg/m2.[1] In recent decades, obesity has been an increasingly severe problem worldwide, with its relation to a range of diseases being constantly discovered, including most cardiovascular diseases, multiple metabolic diseases and over 13 types of cancers, notably shrinking life span.[2]

Yet no country by far has been successful in controlling incidence of obesity. It is predicted that by 2022, over a fifth of world population will have to face the problem of obesity, according to WHO.[3]

China, as a rapidly developing country, has experienced a sharp increase in obesity rate, presumably due to an improvement in income. [4]Nevertheless, a heath concept failing to progress as fast may also play a part.

Another consequence of outdated health concept is that people tend to omit the harm of obesity. Only a limited portion of obese people visit doctors in pursuit of a solution, usually either when symptoms of the complications begin to emerge or when the tendency of deterioration becomes more than obvious, both of which are too late for efficient treatment. So, it would be helpful to develop a handy system that helps to maintain a lower BMI for people with potential obesity problems.

Various factors lead to overweight and obesity problems. Among them is over consumption of fat. Researches have shown relations between diet pattern and bodyweight change (Fig. 1). Otherwise, it is as important to enhance consumption of excess fat tissue of people with higher BMI. In recent years, it has been revealed by multiple studies that taking up short chain fatty acids (SCFAs) conducts a notable change in body weight, both of mice and humans. These facts enlighten us to propose a solution to obesity problems using two combined strategies.

Fig.1 Relations between diet pattern and bodyweight change


Our solution

This year, BNU-China proposes to develop a Synthetic Leanness-promoting Intestinal Microbe (SLIM) that colonizes inside human intestine and promotes catabolism of fat, both assimilated and unassimilated, using two individual pathways. One of them constantly enhances β-oxidation of excessive high fatty acids consumed by human, while the other leads to overproduction of acetic acid, which as a signal, promotes the consumption of human white fat tissue. Out of which the latter is put under the control of a sensing module that enables it to be activated only at optimal time, preventing interference with digestion caused by acidification.

1. Why intestinal microbe?

In recent years, researches have been continuously discovering relations of intestinal microorganisms to human health. It has been revealed that intestinal microbe affects both physical and mental well-being of human in various ways, such as substance metabolism, biological barrier, immune regulation and host defense. All these findings enlighten to find a solution to obesity through intestinal microbe.

More importantly, obesity itself has an inseparable relation to human digestive system, of which intestine is a most important part. By colonizing engineered bacteria with designed traits inside human intestine, we intervene the process of absorption in a most direct way.

In addition, we attempt to develop an intelligent biofactory which automatically regulates its own behavior as its outer environment changes and saves the trouble of taking medicine. Such a design can potentially provide inspirations to others who seek to improve human health by similar means.

2. Overall design

Our circuit is composed of following modules: an acetate producing module to help people consume fat that has already been assimilated, a β-oxidation enhancing module to reduce absorption of unassimilated fatty acids, a sensor that controls the activation of acetate pathway, a colonization-promoting module and two safety modules, all of which are described in more details in Design.

Later, we further improved our regulatory mechanism by introducing a bilateral switch. Under the control of the sensor, the bilateral switch activates only one of the two pathways at a time, according to the chemical signals inside intestine, saving unnecessary burden and conferring it more potential in modification for different scenarios.

[1] Khan SS, Ning H, Wilkins JT, et al. Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity. JAMA Cardiol. 2018.

[2] Basen-Engquist, Karen; Chang, Maria. Obesity and Cancer Risk: Recent Review and Evidence. Current Oncology Reports. 2010-11-16, 13 (1): 71–76.

[3] World Health Organization. Obesity and overweight fact sheet. WHO Media Cent. 2016.

[4] Zhou B.F. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults—Study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed. Environ. Sci. 2002; 15: 83–96.

[5] Singh RM, Rastogi SS, Verma R, et al. Randomized controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow-up. Br Med J 1992;304: 1015–9.

[6] Hunninghake DB, Stein EA, Dujovne CA, et al. The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. N Engl J Med 1992;328: 1213–9.

[7] Schaefer EJ, Lichtenstein AH, Lamon-Fava S, et al. Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. JAMA 1995;274:1450–5.

[8] Schlundt DG, Hill JO, Popie-Cordle J, et al. Randomized evaluation of a low fat ad libitum carbohydrate diet for weight reduction. Int J Obes Relat Metab Disord 1993;17:623–9.

[9] Siggaard R, Raben A, Astrup A. Weight loss during 12 week’s ad libitum carbohydrate-rich diet in overweight and normal-weight subjects at a Danish work site. Obes Res 1996;4:347–56.

Click to View Our Design

© 2019. All Right Reserved. Design by BNU-China