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This year, our team has concentrated on the escalating issue of obesity among Chinese adolescents. To address this, we are developing a biosynthetic strategy to efficiently produce low-calorie rare sugars, particularly D-tagatose, through the genetic engineering of Escherichia coli (E. coli). D-tagatose is a natural low-calorie sweetener with a minimal effect on blood glucose levels, making it an ideal alternative to conventional sugars in tackling this pressing health challenge.
Our objective is to contribute to the mitigation of the global obesity epidemic by promoting healthier dietary sugars. The following section will provide an overview of the current obesity trends in China and globally, explore the multiple factors contributing to obesity, examine the role of sugar in this context, and explain the rationale for selecting D-tagatose as the focus of our study.

In recent years, the global issue of obesity has become increasingly severe. Based on data from WHO, in 2022, one in every eight individuals worldwide is affected by obesity. This alarming statistic highlights that obesity has emerged as a major global public health challenge, posing a serious threat to human health.
Since 1990, the prevalence of obesity among adults worldwide has more than doubled, while the obesity rate among adolescents has tripled. This rapid increase reflects the combined effects of multiple factors, including lifestyle, dietary habits, and environmental influences. High-calorie, high-fat diets, along with a lack of physical activity, are among the primary drivers of this rising obesity rate.
In 2022, there were 2.5 billion adults (aged 18 and above) classified as overweight globally, among whom 890 million were identified as obese. This means that 43% of adults worldwide are overweight, with 16% suffering from obesity. Such a high prevalence not only raises the risk of cardiovascular diseases, diabetes, and certain types of cancer but also places a heavy burden on healthcare systems.
The problem of obesity among children and adolescents is equally concerning. In 2022, 37 million children under the age of five were classified as overweight. Furthermore, over 390 million children and adolescents aged 5 to 19 were overweight, of whom 160 million were obese. Early-life obesity not only affects children's growth and development but may also lead to persistent health issues in adulthood, such as metabolic syndrome and psychological disorders.
According to the "obesity transition" theory, the global obesity epidemic progresses through four distinct stages, as illustrated in Figure 1.
Stage 1 is characterized by poverty and conflict, with overall obesity rates remaining low. However, obesity begins to gradually increase among wealthy, middle-aged individuals, particularly women, and is more prevalent among adults than children. Many developing countries in South Asia and sub-Saharan Africa are currently in this stage.
Stage 2, as countries experience economic growth, obesity rates continue to rise, still more significantly among adults than children. Women tend to experience a faster increase in obesity rates than men, due to physiological differences in fat storage. However, men also begin to gain weight, and there is a noticeable rise in obesity among lower socioeconomic groups. Many countries in Latin America and the Middle East are currently in this stage. High-income countries in East Asia are also at this stage, though they exhibit a lower overall prevalence of obesity.
Stage 3, the gap in obesity prevalence between men and women narrows, and the socioeconomic gradient becomes more evident, with obesity rates rising most rapidly among lower-income populations. At this point, obesity reaches epidemic proportions. Among children and women of higher socioeconomic status, obesity rates tend to stabilize, showing a plateau. Most European countries are currently in this stage.
Stage 4, obesity prevalence begins to decline, typically after a period of stabilization. However, it is important to note that no country has yet demonstrated a consistent decrease in obesity rates or is projected to achieve such a reduction in the near future across its entire population.
Thus, we sadly find that the global obesity problem is intensifying!

Figure 1. The “obesity transition” conceptual framework describing the evolving characteristics of obesity epidemiology in different countries according to the stage of their economic development. HICs high-income countries; SES socioeconomic status
In China, the rates of overweight and obesity across all age groups have been rising rapidly in recent years:

These data illustrate that obesity is a globally prevalent issue, affecting countries across all regions. Over time, the number of obese individuals worldwide continues to increase, emphasizing the need for urgent action to mitigate this public health crisis.
Globally, there has been a significant increase in obesity-induced health problems such as type 2 diabetes, cardiovascular disease, certain types of cancers and musculoskeletal disorders. It is estimated that more than 2.8 million deaths from obesity-related diseases occur globally each year.

So what causes obesity? In order to figure it out, To determine the causes of obesity, our HP team conducted a survey by collecting questionnaires from 213 individuals to understand public awareness of this issue.
Base on our survey, we found that, Consumption of high-calorie diets is identified as the most significant cause of obesity, accounting for 54%. This indicates that the majority of respondents consider the frequent intake of high-calorie foods as the primary factor leading to obesity. And the beverage consumption frequency results also show that most respondents consume sugar-sweetened beverages, such as carbonated drinks and bottled juices, on a daily basis. This high frequency of sugary drink consumption could be a key reason for the high proportion of high-calorie diet intake. Regarding beverage preferences, fruit tea, milk tea, and carbonated beverages are consumed more frequently, while a smaller portion of people indicate that they do not like sugar-sweetened beverages, highlighting the significant influence of dietary habits on obesity.

Figure 2 The survey resluts show that the consumpiton of high-calorie diet especially the frequentlly consuption of sugar-sweetened beverages were related to obesity.

At the same time, we also collected data from Global Obesity Federations. The data also proved that, among these factors, food is one of the most prominent causes of obesity. Meanwhile, the consumption of sugar and sweeteners has the highest correlate of obsesity (Table 1).

Table 1. Sugar intake has the strongest correlation with obesity among the causes of obesity in China.

Then, we also want to know the sugar content in beverages. And then we found this figure 3.The sugar levels are displayed in grams, with each drink's sugar content visually represented by teaspoons (where 5 grams equals one teaspoon). The drinks range from 0 grams of sugar (Valpré mineral water, 500ml) to 44.1 grams (Fanta Grape, 330ml). Many beverages, even those marketed as "healthier" options, like flavored mineral water (Bonaqua flavored water, 330ml) and drinking yogurt (Yogi-Sip apricot flavor, 250ml), contain a high amount of sugar, with values ranging from 19.2 grams to over 44 grams per serving. Popular soft drinks, such as Coca-Cola (35 grams), Sprite (33.7 grams), and various flavors of Fanta, have sugar contents exceeding 30 grams per 330ml serving.Energy drinks and some fruit-flavored beverages, such as Powerade (42.3 grams) and Sparletta Sparberry (39.2 grams), also have a substantial sugar content, often exceeding 40 grams per serving.
The data clearly indicate that many of the beverages available today contain excessively high amounts of added sugar. Even drinks perceived as "healthier" alternatives are not exempt from this, contributing significantly to daily sugar intake. This suggests a need for increased awareness and caution in choosing beverages to avoid excessive sugar consumption, which is a major contributor to obesity and other health issues.

Figure 3. The sugar in papular drinks.

After comparing and analyzing the above factors, we found that controlling calorie intake through diet is a highly effective method for scientifically losing weight. Among the dietary choices, the consumption of sugar sweetened beverages plays a particularly crucial role in weight gain. High-sugar drinks are often loaded with calories while providing minimal nutritional value, leading to an excessive calorie intake. If these extra calories are not burned through physical activity, they are quickly converted into body fat, becoming a major cause of obesity. Therefore, our team has decided to target the reduction of sugary drink consumption as a primary strategy to address the growing obesity problem in modern society.

With growing concerns about excessive sugar consumption and obesity, a variety of alternative sweeteners have been developed to help reduce sugar intake. These include both low- and no-calorie options, ranging from chemically synthesized sweeteners like aspartame and sucralose to naturally derived ones such as steviol glycosides and monk fruit mogrosides. However, replicating other functional properties of caloric sugars, such as texture, browning, and microbial inhibition, remains challenging. Moreover, the use of sugar alcohols, like erythritol, as bulking agents has recently raised concerns due to potential cardiovascular effects. The health implications of many alternative sweeteners continue to be a topic of intense debate.
Among all the sugar subsitute, we found that tagatose stands out among alternative sweeteners due to its unique combination of properties:


In summary, tagatose has multiple advantages over saccharin, sucralose, and allulose. These include chemical properties closer to sucrose, a lower glycemic index, better flavor characteristics, and notable physiological activity and health benefits. These advantages make tagatose highly promising in the food industry, providing consumers with a healthier and more sucrose-like alternative. This is why we chose to study D-tagatose to address the obesity problem.

Considering the increasingly serious issue of obesity today, which severely affects people's health, we recognize that this is a problem that needs to be addressed urgently. At the same time, relevant research has found that excessive sugar intake is a major cause of obesity, and most supermarket fast food products add excessive sugar to enhance their flavor. Although some sugar-free and low-sugar foods have been developed today, their prices are relatively high due to the relatively high production costs of the sugar substitute industry. In recent years, with the rapid development of synthetic biology, research on microbial chassis strains for the large-scale production of sugar substitutes has not only increased production and reduced costs but also been more environmentally friendly. We firmly believe that the large-scale industrial production of sugar substitutes through microbial fermentation has a broad development prospect. By comparing sugar substitutes on the market from multiple aspects, we have chosen D-tagatose, which has high safety and a wide range of functions, for metabolic engineering to enable it to synthesize our target product D-tagatose from glucose. By using E. coli as a fermentation chassis strain, we hope to reduce the environmental pollution caused by large-scale production and create an environmentally friendly and sustainable method for producing high-value sugar substitutes.

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