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Gut bacteria are closely linked to immune functions, review suggests

By Nathan Gray+

30-Sep-2013

Gut bacteria are closely linked to immune functions

A new understanding of the essential role of gut microbes in the immune system could hold the key to battling significant and global public health issues, researchers have suggested.

The review, published in Journal of Allergy and Clinical Immunology , noted that the human gut - and the many microbial species that call it home - play a valuable role in  our own physiological functions, from  digestion and nutrition to immunity.

Led by Dr. Natalia Shulzhenko from Oregon State University, USA, the team noted that a variety of conditions, ranging from autoimmune disease to clinical depression and obesity may be linked to immune dysfunction that begins with a 'failure to communicate' in the human gut.

"New systems biology methods provide essential tools to study this complex system as a whole and to identify key elements that define the crosstalk between the gut microbiota, immunity, and metabolism," said the authors.

"Our intestines contain more immune cells than the entire rest of our body," explained Shulzhenko. "The human gut plays a huge role in immune function."

"This is little appreciated by people who think it's only role is digestion. The combined number of genes in the microbiota genome is 150 times larger than the person in which they reside. They do help us digest food, but they do a lot more than that."

Crosstalk breakdown

An emerging theory of disease, Shulzhenko explained, is a disruption in the 'crosstalk' between the microbes in the human gut and other cells involved in the immune system and metabolic processes.

"In a healthy person, these microbes in the gut stimulate the immune system as needed, and it in turn talks back," she said. "There's an increasing disruption of these microbes from modern lifestyle, diet, overuse of antibiotics and other issues."

"With that disruption, the conversation is breaking down."

Microbiome dysfunction

In the new review, researchers analysed how microbe dysfunction can sometimes result in malabsorption and diarrhea, which affects tens of millions of children worldwide and is often not cured merely by better nutrition.

In contrast, they noted that a high-fat diet may cause the gut microbes to quickly adapt to and prefer these foods, leading to increased lipid absorption and weight gain.

In addition, chronic inflammation, which is linked to most of the diseases that kill people in the developed world today such as heart disease, cancer, and diabetes, may begin with dysfunctional gut microbiota too, they said.

Indeed, Shulzhenko suggested that health care of the future could include a personalised diagnosis of our microbiome in order to determine what prebiotics or probiotics are needed to provide balance.

Moving forward

Shulzhenko noted that an explosion of research in the field of genomic sequencing is for the first time allowing researchers to understand some of this conversation and appreciate its significance.

The results are surprising, she said, with links that lead to a range of diseases, including celiac disease and inflammatory bowel disease. Obesity may be related, too, while some studies have found relevance to depression, late-onset autism, allergies, asthma and cancer.

"Clinical and experimental data indicate that gut function requires a fine balance of cross-regulation between the intestinal epithelium, the immune system, and the gut microbiota," said the authors. "Whether it is immunity or environmental factors that lead to disturbances in lipid metabolism or alterations in lipid metabolism that lead to immune disorders, the microbiota is almost always the one that transmits the signal to other side."

Understanding these processes is a first step to addressing them, Shulzhenko said.

Once researchers have a better idea of what constitutes healthy microbiota in the gut, they may be able to personalise therapies to restore that balance, she added - suggesting that it should also be possible to identify and use new types of probiotics to mitigate the impact of antibiotics, when such drugs are necessary and must be used.

Such approaches are "an exciting target for therapeutic interventions" to treat health problems in the future, the team concluded.

Source: Journal of Allergy and Clinical Immunology
Volume 132, Issue 2 , Pages 253–262, doi: 10.1016/j.jaci.2013.06.025
"Bridging immunity and lipid metabolism by gut microbiota"
Authors: Renee L. Greer, Andrey Morgun, Natalia Shulzhenko

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