Or rewriting the concept of cardiovascular disease prevention and treatment, "Natural Medicine" published Ruijin's blockbuster results: Enterobacteriaceae predict healthy age

Release time:Jun 07, 2024 05:50 AM

In the human intestine, there are trillions of intestinal microorganisms called gut flora. They are deeply involved in various physiological processes of the human body and are closely related to health or disease states.

On June 6, 2024, Beijing time, the National Clinical Research Center for Metabolic Diseases of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the Shanghai Institute of Endocrinology and Metabolism Professors Wang Weiqing and Bi Yufang’s team collaborated with BGI Life Sciences Research Institute and BGI Genomics Zhihui Medical Research Institute published a paper in the journal "Nature Medicine", proposing the concept of "intestinal bacterial age" for the first time, believing that intestinal flora is an important factor in determining human age. This age is not based on human physiological age. In other words, older people with healthy intestinal flora will also look "younger", while unhealthy intestinal flora will make young people "aging" more.

In recent years, more and more studies have proven that intestinal flora is closely related to human aging and metabolism. However, most of the research results so far lack prospective, especially the role of intestinal flora in aging and metabolism, and the lack of in-depth research on the role of cardiovascular disease risk regulation. This study reveals the potential value of intestinal flora in regulating metabolic aging and is expected to provide a new marker for the aging evaluation system.

In addition, the study analysis also found that these "young" flora have a significant regulatory effect on long-term cardiovascular disease in elderly people with metabolic disorders. This means that "intestinal bacterial age" may be able to treat or slow down aging and reduce metabolic-related cardiovascular diseases.

The study collected nearly 20,000 people over the age of 40 with follow-up data for up to 11 years. Taking into account 21 metabolic indicators including obesity, insulin sensitivity, glucose metabolism, lipid metabolism, blood pressure, liver function, kidney function, etc., we pioneered the construction of 5 "metabolic comorbidity subtype clusters", revealing The association between metabolic abnormality subtypes and cardiovascular disease risk. Various metabolic abnormalities can be divided into different types using simple indicators in daily physical examinations. Even if it is the same disease, different metabolic comorbidity subtypes require different treatment methods, providing a basis for precise treatment of metabolic diseases.

These five metabolic comorbidity subtype clusters include: metabolic health cluster, lipid metabolism disorder cluster, obesity and insulin resistance cluster, and glucose metabolism abnormality cluster.

According to 11 years of follow-up, compared with the metabolically healthy cluster, the risk of cardiovascular disease among people in the obesity and insulin resistance cluster and the abnormal glucose metabolism cluster increased by 75% and 117% respectively.

The research team confirmed in another independent validation cohort that clusters of obesity, insulin resistance, and abnormal glucose metabolism were associated with a higher risk of cardiovascular disease. This suggests that cardiovascular health risk can be accurately predicted and managed by identifying individual subtypes of metabolic comorbidities. This study breaks through the previous monotonous single metabolic disease evaluation method and proposes the need to adopt different strategies and individualized management of long-term cardiovascular health for different metabolic subtype clusters, thereby promoting the formulation of precise management plans from groups to individuals.

Younger gut bacteria may reduce disease risk

So what is the subtle relationship between the age of intestinal bacteria and aging, metabolic diseases and cardiovascular diseases?

In the eyes of many people, metabolic diseases and cardiovascular diseases are geriatric diseases that are difficult to avoid with age. Aging indicators that are generally focused on by existing research, such as epigenetic changes, telomere attrition, and proteome homeostasis imbalance, do not consider the role of intestinal microorganisms.

The research team conducted an in-depth analysis of the fecal metagenomic data of 4,491 randomly selected individuals, revealing that the composition of intestinal flora is differentially associated with the age and metabolic status of the individual. Among them, Bacteroidetes was more abundant in younger people, while Prevotella was more common in older people.

Based on 55 age-related intestinal microorganisms, the research team found that in the elderly over 60 years old, even if the metabolic status is seriously disturbed, if the abundance of Prevotella in the intestine of an individual is lower, the age of the intestinal bacteria is "more" Being younger" can significantly reduce the risk of cardiovascular disease. This protective effect has nothing to do with age, gender, education level, lifestyle, eating habits, medication, etc. This shows that intestinal bacterial age, as a biomarker, is expected to predict the risk of cardiovascular disease and become a key marker for regulating metabolic health in aging.

Metabolic disorders and aging are important factors affecting human health. Given my country's huge population, they are also important issues affecting the national economy and people's livelihood. This discovery by the research team may have the potential to control the occurrence of metabolic diseases and cardiovascular diseases from the source.

Professor Wang Weiqing of Ruijin Hospital is the final corresponding author of the paper, Professor Bi Yufang of Ruijin Hospital and researchers Li Junhua and Dr. Zhong Huanzi of BGI are the co-corresponding authors; Researcher Wang Tiange, Researcher Xu Min and Professor Lu Jieli of Ruijin Hospital, Dr. Shi Zhun and Dr. Ren Huahui of BGI are co-author.

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