A large multi-ethnic cohort explores the mystery of human intestinal flora, and Dr. Zhang Xiuying’s team releases the latest research results

Author of this article: Zhang Xiuying, Department of Endocrinology, Peking University People’s Hospital.
Intestinal flora is a dynamically changing system that plays an irreplaceable role in regulating the digestion and absorption of human nutrients, energy metabolism and immune system construction.
Intestinal flora is disordered It is closely related to various diseases such as digestive system diseases, endocrine system diseases, immune diseases and tumors
.

However, in the past 20 years, despite the rapid increase in the number of studies related to the intestinal flora and the endless new discoveries related to it, they are still affected by multiple factors such as sample size, disease and medication, race, region, and eating habits.
The differences and characteristics of intestinal microbes have not been fully described on a population basis
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With the development of new sequencing technologies and the implementation of the Human Metagenomics Project, people have also made more and more in-depth studies on the intestinal flora as the "second genome"
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Based on a Han cohort established by our research team in Pinggu District, Beijing, we collected detailed host metadata and analyzed the gut microbial characteristics of 2,338 community adults aged 26-76 through metagenomic sequencing.
The study on the effect of 88 environmental host phenotypes on the intestinal flora of the Han population in northern China is the largest intestinal metagenomics study of the Chinese population to date, and it is a comprehensive analysis of the structural characteristics of the intestinal flora of the Chinese Han population and its relationship with the host.
The interaction of internal and external environmental factors provides a solid data basis
.

The research team has also integrated nearly 3,000 public intestinal metagenomic data from multiple populations in China, Israel, and the Netherlands, and pioneered the discovery of the relationship between the intestinal flora and gender, sex hormones, age, and various clinical and metabolic parameters
.

The result "Sex- and age-related trajectories of the adult human gut microbiota shared across populations of different ethnicities" was published online in the first issue of "Nature Aging" in 2021, and a review article distributed at the same time gave this work "The study established a regional research cohort with clear characteristics, rich phenotypes, high homogeneity of genetics, geographic location, life>
.

” The comment also pointed out that “homogeneous regional queues and rigorous multi-confounding factor control models are more sensitive and accurate in analyzing human microorganisms.
The key to the rule of group-host interaction has important guiding significance for future microbiome research
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"The study has four core findings: 1.
Gender has the strongest influence on the intestinal flora of the Pinggu population.
Researchers first assessed and pointed out The effects of common metabolic disease drugs on the intestinal flora, excluding 597 individuals receiving treatment, and using an analysis cohort of 1,741 untreated individuals to evaluate the interaction of 88 collection phenotypes with the intestinal flora of the Pinggu population, revealing Seventeen types of phenotypes such as gender, age, androgens, triglycerides, uric acid, obesity, and life>
.

Figure 1 Host external and internal factors related to intestinal microbes.
2.
Gender differences in the intestinal flora of multi-ethnic populations in China and foreign countries.
The latter gender is still significantly related to the intestinal flora in the Pinggu population
.

In order to further verify whether the gender difference in intestinal flora is universal to the population, the research team collected and verified about 3000 cases of intestinal flora data sets from high-quality research cohorts in China, Israel, and the Netherlands
.

Although there are huge differences in genetics, living habits, diet, diversity and structure of intestinal flora among different ethnic groups, the study identified for the first time that the adult intestinal flora has a consistent gender difference: women have higher bacteria than men.
Group diversity; females are significantly enriched than males, including Akkermansia muciniphila, Alipis shahii and other metabolic protection bacteria
.

Figure 2 Chinese and foreign multi-ethnic intestinal microbial characteristics and shared gender differences 3.
The dynamic age trajectory of the gender differences in the intestinal flora is consistent with the changes in sex hormones.
To further explore when the gender differences in human intestinal flora appear and whether they are stable, research The team divided Pinggu and the verified population into the young and middle-aged group (≤50 years old) and the middle-aged group (>50 years old, the average age of women at menopause) according to the age of 50, and the intestinal flora of Dutch children aged 6-9 years was used as a minor control group
.

Grouping analysis reveals that the gender difference in intestinal flora changes dynamically with age, and its difference is consistent with the change trend of sex hormone levels between the sexes.
It is shown as: there is no obvious gender difference in young adults; the most obvious gender difference in young adults; middle-aged and elderly people increase with age (menopause Later) gender differences gradually weakened, and most of the differences disappeared
.

The results of this series of studies indicate that sex hormones play an important role in the establishment and maintenance of gender-related intestinal flora characteristics
.

Figure 3 Age dynamics of sex hormones and intestinal microbial gender characteristics.
4.
Chinese and foreign multi-ethnic human intestinal flora share common aging characteristics.
Finally, after adjusting for gender and other factors, the research team also found that human intestinal flora is multi-ethnic There are a large number of consistent aging characteristics among the cohorts, including higher bacterial diversity, ectopic and proliferation of various oral microorganisms (such as Streptococcus, Veronella, etc.
) into the intestinal environment, and the reduction of bifidobacteria
.

Using a machine learning model, the researchers also built an efficient prediction model for physiological age based on gut microbes (average error age 8-10 years) in each population for the first time
.

It is worth mentioning that the relative abundance of the intestinal Akkermansia and various Clostridium butyricum and other metabolic protection bacteria in the middle-aged and elderly group is also significantly higher than that of the young group, which is contrary to the results of the aging/disease animal model research.

.

Similar to the contradiction, the androgen levels of elderly men in many domestic and foreign cross-sectional cohorts such as Pinggu were significantly higher than those of young men
.

The results of this series of studies collectively indicate the adverse effects of continued industrialization and urbanization on host health and gut microbes
.

Compared with young people, the higher bacterial diversity, richer metabolic protection bacteria, and higher androgen levels in the elderly population may benefit from a healthier diet, life>
.

Whether the correlation between these intestinal flora and age is a characteristic of aging or intergenerational differences, it still needs to be further verified by long-term follow-up of the population
.

Figure 4 The age characteristics of the intestinal flora of Chinese and foreign multi-ethnic people are common.
The author introduces Dr.
Zhang Xiuying, MD, deputy chief physician
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Now working in the Department of Endocrinology, Peking University People's Hospital, and Peking University Diabetes Center
.

Has long been engaged in clinical, scientific research, teaching and popular science work in endocrinology
.

In 2012, he won the Global Health Scholarship and completed post-doctoral research
.

Participated in the compilation of the "Twelfth Five-Year" National Medical College Undergraduate Planning Textbook "Internal Medicine" 2nd edition, and participated in the translation of "Harrison's Internal Medicine" 19th edition
.

He is also a member of the editorial board of the Chinese edition of the Chinese Journal of Diabetes and Care, and a member of the Standing Committee of the Thyroid Committee of the Beijing Society of Endocrinology and Metabolism
.

Presided over or participated in a number of national-level research topics and international cooperation projects, and published a number of high-impact factor research papers as the first author
.

Article link: Zhang, X.
et al.
Sex- and age-related trajectories of the adult human gut microbiota shared across populations of different ethnicities.
Nat.
Aging 1, 87–100 (2021).
References: 1.
Ober, C .
, Loisel, DA & Gilad, Y.
Sex-specific genetic architecture of human disease.
Nature Reviews Genetics (2008) doi:10.
1038/nrg2415.
2.
Özkurt, E.
& Hildebrand, F.
Lifelong sex-dependent trajectories of the human gut microbiota.
Nat.
Aging (2021) doi:10.
1038/s43587-020-00019-x.