人类肠道微生物的基因组规模代谢建模,以告知合理的社区设计
Juan Pablo Molina Ortiz1,2, Dale David McClure3, Andrew Holmes4,5
1Environment Research Unit, CSIRO Environment, Canberra, Australia.
Gut microbes
|July 21, 2025
概括
设计有针对性的微生物群落可以从耐消化碳水化合物 (DRC) 提升有益的短链脂肪酸 (SCFA) 的产生. 这种方法通过克服个体微生物群的变化来改善肠道健康的治疗干预措施.
科学领域:
- 微生物组研究 微生物组研究
- 代谢工程是代谢工程.
- 计算生物学 计算生物学
背景情况:
- 人的肠道微生物群通过代谢物生产影响宿主健康,特别是从耐消化碳水化合物 (DRC) 产生的短链脂肪酸 (SCFA).
- 使用DRC进行微生物组的治疗调制往往受到微生物群体复杂性和功能变异性的阻碍.
- 基因组规模代谢模型 (GEMs) 提供了对微生物代谢能力的系统层面的了解.
研究的目的:
- 系统地分析人类肠道微生物的碳水化合物代谢,使用AGORA系列的GEM.
- 设计基于目的的微生物群落,以实现可预测和增强的SCFA生产,特别是酸盐.
- 提高基于微生物组的治疗干预措施的有效性.
主要方法:
- 从AGORA数据库中利用基因组规模的代谢模型 (GEM) 来推断微生物碳水化合物消耗和代谢物生产.
- 应用逆生态原理,网络分析和GEM社区建模来设计最小的,有弹性的微生物社区.
- 将设计社区集成到模拟的人类微生物组中,以预测SCFA生产和干预反应.
主要成果:
- 在肠道微生物中,DRC降解能力是罕见的,这表明对干预成功具有特定分类的重要性.
- 代谢物生产概况显示出超出家族分类层次的变化,这使得仅仅基于成分的预测变得复杂.
- 一个设计社区在模拟的微生物群中显著增强了酸盐生产,特别是在基线生产较低的微生物群中.
结论:
- 将GEM与微生物社区设计相结合,可以预测有效的微生物群干预措施.
- 基于目的的社区设计可以克服个体的变化,并保证治疗反应.
- 这种方法有可能通过微生物组调节来开发改善宿主健康的策略.
相关概念视频
Introduction to the Human Microbiota
Microorganisms colonize various regions of the human body, including the mouth, nasal passages, throat, stomach, intestines, urogenital tract, and skin. The total number of microbial cells is estimated to range from 10¹³ to 10¹⁴—comparable to, or exceeding, the number of human somatic cells. This host–microbiome relationship has led to the conceptualization of humans as supraorganisms, wherein microbial communities perform vital roles in development, immunity, and disease...
Microbiota of the Large Intestine
The large intestine hosts the most densely populated microbial ecosystem in the human body. This complex community primarily consists of anaerobic bacteria, with Bacillota (formerly Firmicutes) and Bacteroidota (formerly Bacteroidetes) as the predominant groups. The distribution of these microbes varies along different sections of the large intestine, influenced by local environmental factors such as oxygen availability and nutrient composition.The cecum, located at the beginning of the large...
Functions of the Gut Microbiota
The gut microbiota includes trillions of microorganisms that colonize the human gastrointestinal tract, including bacteria, archaea, viruses, and fungi. This complex ecosystem plays a critical role in maintaining intestinal and systemic health. Most of these microbes inhabit the large intestine, establishing a relatively stable and diverse community that contributes to gut homeostasis through various metabolic, immunological, and protective mechanisms.Dominant bacterial phyla, such as...
Dysbiosis of the Gut Microbiota
The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
Gut-Brain Axis
The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...
Microbiota Modulation by Antibiotics
Antibiotics have revolutionized modern medicine by saving countless lives from bacterial infections. However, their widespread use has inadvertently harmed the delicate balance of the human gut microbiota. The gut microbiota, a complex community of bacteria, archaea, viruses, and fungi, plays a vital role in regulating metabolism, immune responses, and maintaining intestinal health. Antibiotics, especially broad-spectrum types, disrupt this ecosystem by eradicating both harmful and beneficial...


