Professor Liping Zhao: Dysbiosis of the core microbiota is the root cause of human obesity！

Professor Liping Zhao

Expert in the field of microbial molecular ecology, Fellow of the American Academy of Microbiology, Distinguished Professor at the School of Life Science and Technology, Shanghai Jiao Tong University, Director of the Laboratory of Microbial Molecular Ecology and Ecological Genomics, and Director of the Nutritional Systems Biology Laboratory at the Shanghai Center for Systems Biomedicine.

(DrugTimes got the authorization from Professor Zhao, many thanks!~)

Dysbiosis of the core microbiota is the root cause of human obesity. This conclusion stems from our team’s 20 years of continuous research, supported by hundreds of international research papers. My personal weight loss journey is also the best testament to this discovery.

The so-called core microbiota refers to the most important gut bacteria affecting our health. Although there are thousands of microbes in the human gut, the core microbiota that has a decisive impact on health actually accounts for less than 10% of the total gut members. These core microbiota are divided into two major camps: one is called the cornerstone microbiota, which we can also call the “big tree” microbiota. They are like the big trees that make up a forest, stabilizing the structure of the microbiota and supporting our health. The other is the pathobiont microbiota, which we can also call the “weed” microbiota. Although the name does not sound very good, it played an important role in helping humans survive famines over millions of years of evolution. However, in modern society with abundant food, pathobionts have become the culprit of obesity and metabolic diseases.

In ancient times, food scarcity was the norm, and prolonged famines forced humans and gut microbiota to evolve together to cope with this huge survival challenge. At that time, the human diet was mainly plant-based, with daily dietary fiber intake reaching 200-400 grams, whereas in modern times, for example, the average daily dietary fiber intake of American adults is only 15 grams. This drastic decrease in dietary fiber intake, coupled with high-calorie diets, completely disrupted the healthy balance of the gut microbiota that had evolved over millions of years.

In ancient times, if dietary fiber content in our diet was high and abundant, it indicated that total food calories were insufficient. At this time, the big tree bacteria dominated, fermenting dietary fiber into acetic acid and butyric acid to provide energy. At the same time, acetic acid and butyric acid would stimulate the secretion of two hormones from the L cells in the gut: GLP-1, which gives us a sense of fullness, and PYY, which gives us satisfaction. When both a sense of fullness and satisfaction occur simultaneously, we naturally stop eating. This mechanism helped ancient humans control their appetite and conserve energy when food was scarce.

However, when dietary fiber decreases and high-calorie diets become dominant, weed bacteria rise rapidly, and the situation is completely different. First, they secrete endotoxins that trigger systemic inflammation, leading to insulin resistance. As a result, we become hungrier and have to eat a lot to relieve our hunger. Second, they release indoles and hydrogen sulfide, inhibiting the secretion of GLP-1 and PYY from L cells. The insufficient secretion of these two hormones means that a sense of fullness and satisfaction is delayed, resulting in overeating. What’s worse, they shut down the genes that burn fat and activate the genes that synthesize fat, quickly converting excess calories into fat and storing it. The core purpose of all these mechanisms is to prepare for the next possible famine. In ancient times, this mechanism helped humans survive famines. However, in modern society, where diets are low in dietary fiber and high in calories, weed bacteria dominate for a long time, and our gut microbiota is always on standby, desperately making us eat more and store more fat, resulting in obesity becoming a common problem in modern society.

What’s more serious is that this long-term pattern of inflammation and fat storage not only causes obesity but also leads to diabetes, cardiovascular diseases, and a series of other metabolic diseases. Therefore, the seesaw model of the core microbiota we propose can fundamentally explain the causes of obesity: when the big tree bacteria dominate, human metabolism is healthy and stable; when the weed bacteria dominate, human metabolism is out of balance, fat storage is excessive, chronic inflammation persists, and obesity and related diseases follow.

Therefore, the key to solving the obesity problem is not a simple matter of eating less and exercising more. There are two very important reasons: First, dysbiosis of the core microbiota makes you feel extremely hungry, and a sense of fullness and satisfaction is delayed, making it difficult to control your appetite with willpower alone. Second, fat storage is hard to consume, and the genes that burn fat are turned off, only being mobilized when life is threatened, to put it bluntly, only when you are on the verge of starvation does the body use these stored fats. Therefore, the real solution is through precise nutritional intervention to support the growth of the big tree bacteria, allowing the cornerstone functional group to regain dominance in the gut. Only in this way can we fundamentally improve metabolism and solve the problems of obesity and diabetes.

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