The Microbiome - Research in Gut Bacteria and Health

image via Microbiology

Over the last 20 years, research into microbiota--the collection of microorganisms, or microbiome, that resides within various tissues of the body--has focused intensely on the gut microbiome and its impact on health and disease.

Here is an overview from Wikipedia:

The human microbiota is the aggregate of microorganisms, a microbiome that resides on or within a number of tissues and biofluids, including the skin, mammary glands, placenta, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, and gastrointestinal tracts. They include bacteria, fungi, and archaea [single-cell prokaryotes]. Micro-animals which live on the human body are excluded. The human microbiome refers to their genomes.[1]

Humans are colonized by many microorganisms; the traditional estimate was that humans live with ten times more non-human cells than human cells; more recent estimates have lowered that to 3:1 and even to approximately the same number; all the numbers are estimates.[2][3][4][5] Some microbiota that colonize humans have not merely a commensal (a non-harmful coexistence), but rather a mutualistic relationship with their human hosts.[1]:700[6] Conversely, some non-pathogenic microbiota can harm human hosts via the metabolites that they produce, like trimethylamine.[7][8] Certain microbiota perform tasks that are known to be useful for the human host; for most, the role is not well understood. Those that are expected to be present, and that under normal circumstances do not cause disease, are deemed normal flora or normal microbiota.[1]

The Human Microbiome Project took on the project of sequencing the genome of the human microbiota, focusing particularly on the microbiota that normally inhabit the skin, mouth, nose, digestive tract, and vagina.[1] It reached a milestone in 2012 when it published initial results.[9]

It has become increasingly common for researchers to distinguish between the microbiome (the collective genomes of the microorganisms residing in an environmental niche, such as the gut) and microbiota (the microorganisms themselves). For the purposes of this research review, most articles are discussing the microbiome in general, and not specific microbiota.

Much of human research has focused on the gut microbiome, or gut flora.

Gut flora (gut microbiota, or gastrointestinal microbiota) is the complex community of microorganisms that live in the digestive tracts of humans and other animals, including insects. The gut metagenome is the aggregate of all the genomes of gut microbiota.[1] The gut is one niche that human microbiota inhabit.[2]

In humans, the gut microbiota has the largest numbers of bacteria and the greatest number of species compared to other areas of the body.[3] In humans the gut flora is established at one to two years after birth, and by that time the intestinal epithelium and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms.[4][5]

The relationship between some gut flora and humans is not merely commensal (a non-harmful coexistence), but rather a mutualistic relationship.[2]:700 Some human gut microorganisms benefit the host by fermenting dietary fiber into short-chain fatty acids (SCFAs), such as acetic acid and butyric acid, which are then absorbed by the host.[3][6] Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics.[2][6] The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ,[6] and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions.[3][7]

The composition of human gut flora changes over time, when the diet changes, and as overall health changes.[3][7] A systematic review from 2016 examined the preclinical and small human trials that have been conducted with certain commercially available strains of probiotic bacteria and identified those that had the most potential to be useful for certain central nervous system disorders.[8]

With that introduction, here are a few recent articles on the advances being made in understanding the power and the potential of the gut microbiome.

Gut microbiome contributes to Parkinson's, study suggests

Written by Honor Whiteman
Published: Friday 2 December 2016

In recent years, researchers have uncovered a wealth of information about how the gut microbiome - the population of microorganisms in the intestines - affects our health. Now, for the first time, scientists reveal how gut microbes may play a key role in Parkinson's disease.

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Circadian Rhythms Regulated By Gut Microbiome

Milla Bengtsson 

December 3, 2016

Even the microbes living inside you have a daily routine. They start their day like clockwork, in one part of the intestinal lining, move a few micrometers to the left, maybe the right, and then return to their original position.

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Chronic fatigue and the microbiome

By Sadja Greenwood, M.D.

12/01/2016

There is tremendous interest in the relationship between the microbes in and on our bodies and our state of health and disease. The origins of chronic fatigue syndrome have remained mysterious, though studied, for years, but it is now believed to be related in some ways to the bacteria in our gut.

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The microbiome, nutrition and the future of health

Maria Fernandez-Guajardo
Dec. 2, 2016

Editor's note: Maria Fernandez-Guajardo is the vice president of product at Clear Labs where she leads product strategy, product delivery, and sales enablement. She has used her strength in emerging technologies, data analytics and passion for making an impact in pioneering food analytics with Clear Labs. 

There is no such thing as the average patient, and there is no such thing as a one-size-fits-all approach to our health. Fortunately, we’ve reached a point in history when precision medicine – a groundbreaking approach to disease prevention and treatment based on people’s individual differences in environment, genes and lifestyle – is a reality.

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Gut microbes switch host genes on and off under influence of diet

Written by Catharine Paddock PhD
Published: Friday 25 November 2016

New research provides further evidence of the important role that gut microbes play in health - by revealing they alter host gene expression in a diet-dependent manner. Using mice, the researchers show a Western diet prevents many of the gene expression changes of a plant-rich diet.

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Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues

Kimberly A. Krautkramer, Julia H. Kreznar, Kymberleigh A. Romano, Eugenio I. Vivas, Gregory A. Barrett-Wilt, Mary E. Rabaglia, Mark P. Keller, Alan D. Attie, Federico E. Rey, John M. Denu 

Highlights
• Gut microbiota alter host histone acetylation and methylation in multiple tissues
• Western diet suppresses microbiota-driven SCFA production and chromatin effects
• SCFAs recapitulate microbiota-driven chromatin and transcriptional effects 

Summary
Histone-modifying enzymes regulate transcription and are sensitive to availability of endogenous small-molecule metabolites, allowing chromatin to respond to changes in environment. The gut microbiota produces a myriad of metabolites that affect host physiology and susceptibility to disease; however, the underlying molecular events remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues in a diet-dependent manner: consumption of a “Western-type” diet prevents many of the microbiota-dependent chromatin changes that occur in a polysaccharide-rich diet. Finally, we demonstrate that supplementation of germ-free mice with short-chain fatty acids, major products of gut bacterial fermentation, is sufficient to recapitulate chromatin modification states and transcriptional responses associated with colonization. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health.

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Scientists uncover genetic evidence that 'we are what we eat'

Date: November 15, 2016

Source: University of Oxford

Summary: Researchers have demonstrated that the diets of organisms can affect the DNA sequences of their genes.

Researchers at the University of Oxford have demonstrated that the diets of organisms can affect the DNA sequences of their genes.

In a study on two groups of parasites, the team detected differences in DNA sequences that could be attributed to the composition of their food.

The results are published in the journal Genome Biology.

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Eat lots of fiber or microbes will eat your colon

Posted by Kara Gavin-U. Michigan
November 20th, 2016

It sounds like the plot of a 1950s science fiction movie: normal, helpful bacteria begin to eat their host from within, because they don’t get what they want.

But that’s exactly what happens when microbes inside the digestive system don’t get the natural fiber that they rely on for food.

Starved, they begin to munch on the natural layer of mucus that lines the gut, eroding it to the point where dangerous invading bacteria can infect the colon wall.