Diet Effects on Gut Microbiome Composition, Function, and Host Physiology


Abbreviations

DIO

diet-induced obesity

FFA

free fatty acid

FOS

fructo-oligosaccharides

GOS

galacto-oligosaccharides

HFD

high fat diet

HMO

human milk oligosaccharides

LPS

lipopolysaccharide

PBA

primary bile acid

RYGB

Roux-en-Y gastric bypass

SBA

secondary bile acid

SCFA

short-chain fatty acid

WD

western diet

Introduction

Diet has long been implicated in a suite of specific physiological outcomes in the host, ranging from obesity, to cancer, to risk of infectious disease. The advent of readily accessible next-generation sequencing (NGS) platforms in the last 15 years has revealed that diet can affect the composition and functionality of microbes in the gut. Targeted mechanistic studies of these changes have revealed that many of the well-described effects of diet on host physiology have substantial microbial underpinning, suggesting that the gut microbiota—the collection of microbes in the gut—is a vector for diet to exert physiological changes in the host.

Diet is considered as one of the three major effectors of host microbial structure, which along side host genetics, and early life exposures, are responsible for the assembly and subsequent composition of our gut microbiota. Factors like our method of delivery, whether we are breast fed or formula fed, and when we were first exposed to antibiotics interact with host-genetic pressures to set the foundation for what will ultimately become the homeostatic microbial associations that we maintain for the duration of our lives. However, diet has the capability to modulate that foundation and has been shown to trump host genetics with respect to phenotypic outcomes. The diet plays a critical role in regulating the relative abundance and activity of the bevy of microbes that live in and on us. Diet-induced microbiome changes occur rapidly, in as few as 4 days, and the effects are readily reversible in the short term. However, long-term effects of diet on microbial community structure have also been noted. Cultural dietary norms tune baseline microbial composition to fit the dietary preferences of populations and given sufficient generational exposure, diet can lead to irreversible microbial extinction events. Extinctions are not only difficult to rectify, but the reduction in microbial diversity due to long-term dietary pressure can have negative long-term outcomes for the host. As such, we must pay careful attention to our diets and their resulting effect on microbes in the gut. To begin to understand the effect of diet on the gut microbes and host physiology we must first explore the tools that are available to investigate these systems.

Techniques to Assess Effects of Diet on Microbial Composition and Functionality

Compositional Tools—Culture Based

Early studies on dissecting the microbiota were compositional or survey experiments. The so-called “who's there” studies. Forays into this field were once technologically limited to culture-based techniques, which relied on an array of specialized growth mediums in varying conditions to identify the specific microbes. Expensive and time consuming, this paradigm is also restricted to a small subset of organisms for which established culture conditions have been described. This limited our insight to < 20% of what is present in most environments. As a result, locations with limited diversity and those enriched in difficult or impossible to culture resident organisms were considered sterile. The urinary tract is a prime example. Once considered sterile outside of infection, we now appreciate the urinary tract has a complex and dynamic microbial association. Nearly all locations in the body now have described resident microbes, and there is great diversity in composition and function based on location. This revelation is the direct result of the development of culture-independent sequence-based identification methodologies, which greatly enhance the extent by which we can probe composition.

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