Everyone in this era is on the way to struggle. Nowadays, the great pressure from study, work, family and other parties stimulates the resistance of more and more people’s body, which leads to the appearance of some symptoms such as overwork, anxiety and insomnia.

" I'm up to my eyeballs in work, and I don't have time to prepare my own meals. I either eat fast food or skip breakfast and lunch until I have a big meal in the evening. I can't get rid of this unhealthy diet, and my weight remains high. Not only that, but I also have to bear the pressure of work—working overtime! My health is no longer good, my whole body is weak and it is difficult to fall asleep. I don't know when I will fall down. I am really too tired. "

"In order to successfully go ashore for the postgraduate entrance examination, I can only study day and night. Under great pressure, I am often irritable and anxious, sweet food is the only consolation in the bitter sea of my life. But I am already overweight. What should I do? The doctor advised me to eat less food with high sugar and fat content and exercise more. But I can't insist that long at all! "

"Every time I am unhappy, I eat a lot of food to comfort myself. After I started working, all varieties of failures and setbacks caused me to resist pressure by overeating. Snacks were the first thing I thought of when I was in trouble sleeping every night. Now, emotion and weight are the last two words I want to mention. "

"Obesity from overwork " is a phenomenon that people who work busier are more likely to get fat because of too much stress, irregular diet and frequent staying up. The main reasons leading to overwork are:

Lack of sleep.
Sleeping less or staying up all night will result in an increase in hunger hormones in the blood, which will bring about obesity. If you don't sleep at night, you are more likely to overeat and get " obesity from overwork ". Lack of sleep will not only make people slow down their movements, but also slow down their metabolism, causing them to consume less energy and gain weight.

Disorder of hormone secretion.
Heavy work gives rise to the increasing of people's psychological pressure. When the body receives the signal of excessive pressure, it will release more anti-stress hormones, which will make the blood sugar and blood pressure rise and produce fat. What’s more, it will increase the secretion of cortisol (a glucocorticoid) and the accumulation of fat to the waist and abdomen, buttocks, back; It will decrease the thyroid hormone level and disturb the metabolism of the body.

Unscientific diet.
Most people don’t have a healthy diet, do not exercise enough, and sit and work for a long time every day, including children, teenagers and adults who use computers for a long time. Obesity or overweight is inevitable.

Our days are too hectic. Everyone is carrying a heavy load, and not everyone will effectively relieve the pressure. As college students, we are busy running for growth, while other adults in the society have to be busy and anxious for other things. Gradually, some people take the pressure and anxiety to the road of overweight.

From a scientific point of view, excessive fat accumulation in human body will affect people's digestive system, endocrine system, cardiovascular system and nervous system. Compared with ordinary people, these people are more likely to contract diseases such as hypertension, hyperlipidemia, coronary heart disease, asthma, etc., and at the same time, the probability of suffering from cancer is greatly increased. Once a person's weight exceeds the normal range, it is necessary to take certain intervention measures!

Many people face the ever-increasing accumulation of fat, and the first choice is diet pills. Nowadays, in the face of huge market demand, various weight-reducing drugs emerge in endlessly, and the weight-reducing products on the market generally contain hormone components, appetite suppressant components, grease decomposition suppressant components and so on. Taking hormones for example, it achieve the purpose of losing weight by ingesting hormones, inhibiting the stimulation of sympathetic nerves by food, and promoting gastrointestinal peristalsis. However, these weight-reducing drugs uaually have certain side effects, which often bring about endocrine disorders, insomnia, palpitations, vomiting and diarrhea, etc.

Ideal weight-loss products should not only help people lose weight, but also alleviate the pain caused by weight-loss process. Unfortunately, most weight-loss drugs on the market do not have ideal effects, while their side effects will bring people anxiety.

Maybe you are very anxious of your "sub-health" state, or you are overweight because of stress and anxiety. When you feel stressed and want to get rid of anxiety, don't worry, our team has constructed a kind of E. coli probiotics by genetic engineering, which may help solve your troubles and help you gradually change this dilemma.

Alleviating overwork and excessive anxiety, which involve two major problems of intestinal tract and nervous system, we consider the brain-gut axis theory. Broadly defined, the brain-gut axis includes central nervous system, central endocrine system and central immune system, including hypothalamic-pituitary-adrenal axis (HPA axis), sympathetic nervous system, parasympathetic nervous system (vagus nerve) and enteric nervous system in autonomic nervous system, and intestinal microorganisms.

In the past few years, more and more studies have indicated that a change in the interaction between brain and intestine axis is related to functional bowel disease, chronic abdominal pain and even eating disorders. The change of brain axis function is related to stress response and behavior change. There is a high correlation between stress-related mental symptoms such as anxiety and irritable bowel syndrome.

From the current research, we can clearly learn that the intestinal tract does affect human emotions. Having a healthy intestinal tract can make people feel comfortable, while an unbalanced intestinal tract environment may induce anxiety, depression and autism. Therefore, the starting point of solving the problem is to make intestinal probiotics and improve the intestinal environment, so as to help alleviate the problems of overwork and anxiety caused by high pressure.

By taking it orally, this probiotic will enter your intestinal tract, break down fat into glycerol and fatty acids, help regulate diet balance, absorb oil and reduce the risk of diseases like hypertension. Then, using the small molecular precursors produced by them to synthesize new substances-γ-aminobutyric acid (GABA) and 5- hydroxytryptophan (5-HTP). Our E.coli can not only relieve your weight gain, but also produce GABA and 5-HTP, which can help you reduce anxiety, prevent depression, promote melatonin formation, improve sleep quality and even suppress appetite.

We hope our research can help you to relieve stress and anxiety, take away excess fat in your body, bring you happiness and health, and bring more pleasure and relaxation to the world!

Part 1: Boost consumption of fatty acids by enhancing beta-oxidation
To render E. coli to absorb more fatty acids, we increase the expression of FadL (long-chain fatty acid transporter protein) on the surface and FadD (acyl-CoA synthetase).

Part 2: Biosafety: kill switch using toxin-antitoxin system
1)Express antitoxin MazE under the control of the vgb promoter, which is only on under microaerophilic conditions.

2)The expression of the toxin MazF is induced by dietary lactose. Under microaerophilic conditions in the human intestine, engineered bacteria will survive by expressing the antitoxin MazE. However, once bacteria are excreted to the aerobic environment, MazE will no longer be produced, causing bacteria to commit suicide.

3)To test the function of the toxin, mazF will be controlled under an inducible promoter.

Figure. 1 toxin-antitoxin system

Part 3: 5-HTP synthesis and its regulation
1)By employing the E. coli endogenous phenylalanine 4-hydroxylase (P4H) and replacing the P4H cofactor BH4 with MH4, we improved the conversion rate from tryptophan to 5-HTP.

2)5-HTP production needs to be controlled as the engineered bacteria are residing in the human intestine. We therefore deleted the SerA pathway to limit 5-HTP synthesis by reducing the amount of its precursors.

Figure. 2 Producing 5-HTP

Figure. 3 Regulation of synthesizing 5-HTP

Part 4: GABA synthesis and its regulation

Figure. 4 Producing GABA

The whole BUCT team would like to thank our sponsors. Especially:
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Address: No.15 North Third Ring East Road,Chaoyang District,Beijing,P.R.China. Beijing University of Chemical Technology