Stanford scientists use dietary seaweed to manipulate gut bacteria in mice

May 09, 2018

Gut bacteria thrive on the food we eat. In turn, they provide essential nutrients that keep us healthy, repel pathogens and even help guide our immune responses.

Understanding how and why some bacterial strains we ingest can successfully take up residence in the large intestine, while others are quickly evicted, could help scientists learn how to manipulate the makeup of thousands of bacterial species there in ways that enhance our health or help fend off disease. But the sheer complexity of gut ecology has hampered this task.

Now, researchers at the Stanford University School of Medicine working with laboratory mice have shown that it's possible to favor the engraftment of one bacterial strain over others by manipulating the mice's diet. The researchers also have shown 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 in a chaotic manner during our first few years of life," said Justin Sonnenburg, PhD, 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 in a deliberate manner to enhance health and fight disease."

A paper describing the research will be published online May 9 in Nature. Sonnenburg is the senior author. Former graduate student Elizabeth Shepherd, PhD, is the lead author.

Giving bacterium a leg up

The burgeoning field of probiotics -- live, presumably healthful bacterial cultures naturally found in food such as yogurt or included in over-the-counter oral supplements -- is an example of a growing public awareness of the importance of gut bacteria. Even if you don't take probiotics or eat yogurt, however, each of us unknowingly consumes low levels of gut-adapted microbes throughout our life. But, regardless of the source, it's not known what causes one strain to be successful over another. Many pass quickly through our digestive tract without gaining a foothold in our teeming intestinal carpet.

Sonnenburg and his colleagues wondered whether a dietary boost would give specific bacterial strains a leg up in the wild west of the gut microbiome. To investigate, they trekked to 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 are able to digest an ingredient relatively rare in American diets: the seaweed called nori used in sushi rolls and other Japanese foods. They screened the bacteria collected in the primary effluent for an ability to use a carbohydrate found in nori called porphyran.

"The genes that allow a bacterium to digest porphyran 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.

A direct effect

The researchers found that when the mice were fed a typical diet of mouse chow, the porphyran-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 porphyran-rich diet, the results were dramatically different: The bacteria engrafted robustly at similar levels in all the mice. Furthermore, Shepherd found that she 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 porphyran 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. "Porphyran-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."

The researchers also envision developing bacteria that harbor kill switches and logic gates that will permit clinicians to toggle bacterial activity on and off at will, or when a specific set of circumstances occur.

"It's become very clear over the last 10 years that gut microbes are not only wired to many aspects of our biology, but that they are also very malleable," Sonnenburg said. "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."
-end-
Stanford graduate student Kali Pruss is a co-author of the study. Researchers from Novome Biotechnologies also co-authored the study.

The research was supported by the National Institutes of Health (grant DK085025) and the National Science Foundation.

Stanford's Department of Microbiology and Immunology also supported the work.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med.stanford.edu/school.html. The medical school is part of Stanford Medicine, which includes Stanford Health Care and Stanford Children's Health. For information about all three, please visit http://med.stanford.edu.

Stanford Medicine

Related Bacterium Articles from Brightsurf:

Root bacterium to fight Alzheimer's
A bacterium found among the soil close to roots of ginseng plants could provide a new approach for the treatment of Alzheimer's.

Tuberculosis bacterium uses sluice to import vitamins
A transport protein that is used by the human pathogen Mycobacterium tuberculosis to import vitamin B12 turns out to be very different from other transport proteins.

Bacterium makes complex loops
A scientific team from the Biosciences and Biotechnology Institute of Aix-Marseille in Saint-Paul lez Durance, in collaboration with researchers from the Max Planck Institute of Colloids and Interfaces in Potsdam and the University of Göttingen, determined the trajectory and swimming speed of the magnetotactic bacterium Magnetococcus marinus, known to move rapidly.

Researchers show how opportunistic bacterium defeats competitors
The researchers discovered that Stenotrophomonas maltophilia uses a secretion system that produces a cocktail of toxins and injects them into other microorganisms with which it competes for space and food.

Genetic typing of a bacterium with biotechnological potential
Researchers at Kanazawa University describe in Scientific Reports the genetic typing of the bacterium Pseudomonas putida.

How the strep bacterium hides from the immune system
A bacterial pathogen that causes strep throat and other illnesses cloaks itself in fragments of red blood cells to evade detection by the host immune system, according to a study publishing December 3 in the journal Cell Reports.

The cholera bacterium can steal up to 150 genes in one go
EPFL scientists have discovered that predatory bacteria like the cholera pathogen can steal up to 150 genes in one go from their neighbors.

Exploiting green tides thanks to a marine bacterium
Ulvan is the principal component of Ulva or 'sea lettuce' which causes algal blooms (green tides).

The cholera bacterium's 3-in-1 toolkit for life in the ocean
The cholera bacterium uses a grappling hook-like appendage to take up DNA, bind to nutritious surfaces and recognize 'family' members, EPFL scientists have found.

Excellent catering: How a bacterium feeds an entire flatworm
In the sandy bottom of warm coastal waters lives Paracatenula -- a small worm that has neither mouth, nor gut.

Read More: Bacterium News and Bacterium Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.