Paper intensive reading (四)：Establishing What Constitutes a Healthy Human Gut Microbiome

本文链接：https://blog.csdn.net/wxw060709/article/details/103312373

论文题目：Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions

Published: 02 August 2019

McBurney, ..., Jens Latulippe, Marie E.

Published in Journal of Nutrition

Google citation:3

提出的重要问题：Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?

Abstract:

On December 17, 2018, the North American branch of the International Life Sciences Institute (ILSI North America) convened a workshop “Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?” with >40 invited academic, government, and industry experts inWashington, DC. The workshop objectives were to

(1) develop a collective expert assessment of the state of the evidence on the human gut microbiome and associated human health benefits;人类肠道微生物组和相关人类健康益处

(2) see if there was sufficient evidience to establish measureable gut microbiome characteristics that could serve as indicators of "health"; 可测量的肠道微生物特征，作为“健康”的指标

(3) identify short- and long-term research need to fully characterize healthy gut microbiome host relationships; 充分表征健康的肠道微生物组宿主关系的短期和长期研究的需要

(4) publish the findings

Conclusions were as follows:

(1) mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; 回答第一项工作目标，目前可靠的联系并未建立

(2) It is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease; 肠道菌群失调与上皮功能、疾病之间的因果关系不明确。回答第二项目标

(3) microbiome communities are highly individualized, show a high degree of interindividual variation to perturbation, and tend to be stable over years; 微生物群落高度个体化，对微扰表现出高度的个体间变异，多年趋于稳定; 第二项目标，可测量的肠道微生物特征因为个体化差异，所以很难指定。

(4) the complexity of microbiome-host interactions requires a comprehensive, multidisciplinary research agenda to elucidate relationships between gut microbiome and host health; 第三项目标，肠道菌群和宿主之间的关系非常复杂

(5) biomarkers and/or surrogate(替代) indicators of host function and pathogenic processes based on the microbiome need to be determined and validated, along with normal ranges, using approaches similar to those used to establish biomarkers and/or surrogate indicators based on host metabolic phenotypes; future direction

(6) future studies measuring responses to an exposure or intervention need to combine; future direction

(7) Because static genetic sampling misses important short- and long-term microbiome-related dynamic changes to host health, future studies must be powered to account for inter- and intraindividual variation and should use repeated measures within individuals. 静态遗传取样遗漏了重要的短期和长期微生物群落相关的动态变化对宿主健康的影响

Keywords: microbiome, microbiota, prebiotic, probiotic, dietary fiber, biomarker, surrogate indicator, dysbiosis, human health

Outline:

1. Introduction

2. State of the Evidence

3. Biological Considerations in Defining a Healthy Gut Microbiome

4. Infant Microbiome Insights

5. Adult Microbiome Insights

6. Dietary Modulation

7. Probiotic Administration

8. Technical Challenges in Studying Gut Microbiome and Host Interactions

9. Regulatory Considerations with Respect to the Gut Microbiome

9.1 Regulatory considerations in the United States, Canada, and Europe

9.2 Nutrient declarations

9.3 Labeling regulations specific to some dietary fibers and prebiotics

9.4 Structure-function and function claims

9.5 Disease risk reduction claims

9.6 Regulatory considerations in Asia and other regions

10. What Type of Information Is Needed to Define a Healthy Gut Microbiome?

11. What Are Current Limitations to Establishing a Healthy Gut Microbiome-Host Relationship?

12. What Types of Studies Can Address These Gaps?

13. Future Considerations

Content:

1. Introduction

there have been few consistent changes in microbiota stability, resilience, or diversity associated with a given disease across multiple cohorts. 在多个群组中，与某一特定疾病相关的微生物群稳定性、弹性或多样性几乎没有一致的变化。

This article summarizes the state of the science pertaining to the human gut microbiome and associated health benefits and identifies research gaps and opportunities.

2. State of the Evidence

In 2012, the International Life Sciences Institute (ILSI) North American Microbiome Committee commissioned a review on the question “what constitutes a healthy human gut microbiome” that came to the following conclusions:
1) a healthy microbiome cannot be defined by a single idealized community composition, 一个健康的微生物组无法通过单一的社区单元来定义
2) a healthy microbiome is more resistant and resilient to disruption, 一个健康的微生物组抵抗力和可恢复性更强
3) certain microbial distributions may increase susceptibility to infection and disease, 某些微生物分布可能会增加对感染和疾病的敏感性
4) it is unknown if dysbiosis, an imbalance in the types of microorganisms present in a given microbiota, is a cause or consequence of disease. 给定微生物群落的失衡与疾病之间的因果关系不明确
For this article, we revisited the central question and evaluated whether the state of the evidence has changed substantially in the past six years. 对比这个结论和本篇review的结论，我怎么感觉好像没什么进展呢？不明确的还是不明确呢？

3. Biological Considerations in Defining a Healthy Gut Microbiome

In humans, causality is much harder to establish, but environmental factors known to disrupt microbiome assembly [e.g., route of birth delivery, formula vs. breastfeeding, and early antibiotics] are linked with disease risk in epidemiological(流行病学) studies. 在人体中，因果关系很难建立，但是在流行病学中，已经建立了一些连接

In addition, human diseases are often associated with a “dysbiosis” of the gut microbiota, meaning an altered composition or functionality compared with healthy controls. 此外，人体疾病与肠道菌群失调有关联

it is extremely difficult to define what constitutes a healthy microbiome. （1. 因果关系很难确定；2. 有一些发现在不同的研究中不一致）

4. Infant Microbiome Insights

Although these deterministic factors have a clear, measurable impact on microbiome composition, community assembly is also driven by stochastic (nonpredictable) ecological processes. 虽然已知婴儿的肠道菌落跟很多因素有关，但是群落聚集也是受随机的(不可预测的)生态过程驱动。

The early gut microbiota of breastfed, vaginal-born infants is dominated by Bifidobacterium and Bacteroides species, which have evolved with humans and have specialized in the utilization of human milk oligosaccharides(寡糖). These genera could therefore be considered characteristic for a healthy infant microbiota, and they are greatly reduced through cesarean sections(剖宫产) and formula feeding. 双歧杆菌和拟杆菌属被认为是一个健康的婴儿肠道菌群特征

5. Adult Microbiome Insights

相对稳定，更多的受环境因素的影响

Deterministic factors: Nongenetic 10%, genetic factors 10%, specific environmental factors (diet, medication, specific genes, etc.) 20%

High microbiota diversity seems to be associated with health and temporal stability, and a dynamic loss of diversity may be prognostic of increased disease risk.

Remarkably stable microbial community in healthy adults
composed of highly adapted microbial species and shaped more by environment than host genetics
Deterministic factors: Nongenetic 10%, genetic factors 10%, specific environmental factors (diet, medication, specific genes, etc.) 20%
the majority of interindividual variation in the human gut microbiota unexplained
High microbiota diversity seems to be associated with health and temporal stability, and a dynamic loss of diversity may be prognostic of increased disease risk.
The gut microbiome is altered in various diseases, a state often referred to as dysbiosis
it is unclear if dysbiosis are the cause of the disease or just a consequence
microbiome is affected by many characteristics of the host, including ethnicity, region of habitation, geography, and/or socioeconomic status
Regional variation limits the development and application of healthy microbiome reference ranges

6. Dietary Modulation

7. Probiotic Administration

8. Technical Challenges in Studying Gut Microbiome and Host Interactions

9. Regulatory Considerations with Respect to the Gut Microbiome

9.1 Regulatory considerations in the United States, Canada, and Europe

9.2 Nutrient declarations

9.3 Labeling regulations specific to some dietary fibers and prebiotics

9.4 Structure-function and function claims

9.5 Disease risk reduction claims

9.6 Regulatory considerations in Asia and other regions

10. What Type of Information Is Needed to Define a Healthy Gut Microbiome?

11. What Are Current Limitations to Establishing a Healthy Gut Microbiome-Host Relationship?