11 May 2018 --- US researchers examining how to manipulate gut bacteria to boost essential nutrients for better health have been “blown away” by the results they got when using dietary seaweed in mice.

Gut bacteria thrive on the different types of food consumed, providing essential nutrients that keep people healthy, repel pathogens and guide immune responses. However, much remains unknown about how some bacterial strains that are ingested can successfully take up residence in the large intestine, while others are quickly evicted.

Learning more about how to manipulate the makeup of thousands of bacterial species there in ways that enhance health and help fend off disease, is what scientists at Stanford University School of Medicine have been doing.

It’s a difficult task given the sheer complexity of gut ecology.

But, the researchers have worked with laboratory mice to show that it's possible to favor the engraftment of one bacterial strain over others by manipulating the mice's diet. They revealed that it's possible to control how much a bacterium grows in the intestine by calibrating the amount of a specific carbohydrate in each mouse's water or food.

“We're all endowed with a microbial community in our guts that assembled chaotically during our first few years of life,” said Justin Sonnenburg, Ph.D., associate professor of microbiology and immunology.

“Although we continue to acquire new strains throughout life, this acquisition is a poorly orchestrated and not-well-understood process. This study suggests it could be possible to reshape our microbiome deliberately to enhance health and fight disease.”

A paper describing the research will be published been published in Nature.

Does seaweed help give bacterium a leg up?
The field of probiotics – live bacterial cultures naturally found in food such as yogurt or included in oral supplements – is one example of growing public awareness of the importance of gut bacteria. However, regardless of the source, it's not known what causes one strain to be successful over another as many passes quickly through the digestive tract without gaining a foothold in the intestines.

Sonnenburg and his colleagues posed the question of whether or not a dietary boost would help give specific bacterial strains bolster the gut microbiome.

The team visited the San Jose Wastewater Treatment Facility to find members of the Bacteroides – the most prominent genus in the human gut microbiota – specifically looking for strains that can digest an ingredient relatively rare in American diets.

This is the seaweed called nori which is used in sushi rolls and other Japanese foods. The researchers screened the bacteria collected in the primary effluent for an ability to use a carbohydrate found in nori called porphyrin.

“The genes that allow a bacterium to digest porphyrin are exceedingly rare among humans that don't have seaweed as a common part of their diet,” Sonnenburg said. “This allowed us to test whether we could circumvent the rules of complex ecosystems by creating a privileged niche that could favor a single microbe by allowing it to exist in the absence of competition from the 30 trillion other microbes in the gut.”

Once they'd found a nori-gobbling strain of Bacteroides, the researchers attempted to introduce it into each of three groups of laboratory mice. Two groups of the mice had their own gut bacteria eliminated and replaced with the naturally occurring gut bacteria from two healthy human donors, each of whom donated exclusively to one group or the other. The third group of mice harbored a conventional mouse-specific community of gut microbiota.

What was the effect?
The researchers found that when the mice were fed a typical diet of mouse chow, the porphyrin-digesting strain was able to engraft in two groups of mice to varying and limited degrees; one of the groups of mice with human gut bacteria rejected the new strain completely.

However, when the mice were fed a porphyrin-rich diet, the results were dramatically different: The bacteria engrafted robustly at similar levels in all the mice. Furthermore, the researchers found they could precisely calibrate the population size of the engrafted bacteria by increasing or decreasing the amount of nori the animals ingested.

“The results of this dilution experiment blew us away,” Sonnenburg said. “The direct effect of diet on the bacterial population was very clear.”

In addition to showing that they could favor the engraftment and growth of the nori-gobbling bacterial strain, the researchers went one step further by showing that the genes necessary to enable the digestion of porphyrin to exist as a unit that can be engineered into other Bacteroides strains, giving them the same engraftment advantage. Now they're working to identify other genes that confer similar dietary abilities.

“We can use these gene modules to develop a vast toolkit to make therapeutic microbial treatments a reality,” Sonnenburg said. “Porphyrin-digesting genes and a diet rich in seaweed is the first pair, but there could potentially be hundreds more. We'd like to expand this simple paradigm into an array of dietary components and microbes.”

“It's become very clear over the last ten years that gut microbes are not only wired to many aspects of our biology but that they are also very malleable,” Sonnenburg continued.

“Our growing ability to manipulate them is going to change how precision health is practiced. A physician whose patient is about to begin immunotherapy for cancer may choose to also administer a bacterial strain known to activate the immune system, for example. Conversely, a patient with an autoimmune disease may benefit from a different set of microbiota that can dial down an overactive immune response. They are just a very powerful lever to modulate our biology in health and disease.”


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