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Dietary Seaweed Used to Manipulate Gut Bacteria in Mice

May 21, 2018

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Nori, roasted sheets of seaweed used in Japanese cuisine for sushi. The smaller ones are already seasoned with sesame oil and spices. Nori is typically toasted prior to consumption (yaki-nori). Part of the toasting process includes umami flavors like soy sauce, and seasonings. It is also eaten by making it into a soy sauce-flavored paste, (nori no tsukudani) Photo credit: Alice Wiegand, (Lyzzy) - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=740793

A paper published online in Nature (9 May 2018), showed in experiments in 1) ___, that it's possible to favor the engraftment of one gut bacterial strain over others by manipulating the diet. The study also showed that it's possible to control how much a bacteria grow in the intestine by calibrating the amount of a specific carbohydrate in the water or food.

Gut bacteria thrive on the 2) ___ 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 in the understanding on how to manipulate the makeup of thousands of bacterial species found there, in ways that enhance our health or help fend off 3) ___. 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 4) ___. The authors 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. According to the authors, we are all endowed with a microbial community in our guts that are assembled during our first few years of 5) ___, and that although we continue to acquire new strains throughout life, this acquisition is a poorly orchestrated and not-well-understood process. The study suggests it could be possible to reshape our microbiome in a deliberate manner to enhance health and fight disease.

The burgeoning field of probiotics, that comprises 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. But even if you don't take probiotics or eat 6) ___, 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. To investigate whether a dietary boost would give specific bacterial strains a leg up in the gut microbiome. The authors went to the San Jose Wastewater Treatment Facility to find members of the Bacteroides -- the most prominent genus in the human 7) ___ 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. The authors screened the bacteria collected in the primary effluent for an ability to use a carbohydrate found in nori called porphyran. Apparently, the genes that allow a bacterium to digest porphyran are exceedingly rare among humans that don't have 8) ___ as a common part of their diet. This allowed the authors to test whether it was possible to 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 a nori-gobbling strain of Bacteroides was identified, the authors 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 9) ___ 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.

Results showed 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, it was possible to precisely calibrate the population size of the engrafted bacteria by increasing or decreasing the amount of nori the animals ingested. In addition to showing that they could favor the engraftment and growth of the nori-gobbling bacterial strain, the authors 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. The authors 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. For example, a physician whose patient is about to begin immunotherapy for 10) ___ may choose to also administer a bacterial strain known to activate the immune system. 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. Sources: Stanford University School of Medicine; Elizabeth Stanley Shepherd, William C. DeLoache, Kali M. Pruss, Weston R. Whitaker, Justin L. Sonnenburg. An exclusive metabolic niche enables strain engraftment in the gut microbiota. Nature, 2018; DOI: 10.1038/s41586-018-0092-4; ScienceDaily, Krista Conger; Wikipedia

ANSWERS: 1) mice; 2) food; 3) disease; 4) diet; 5) life; 6) yogurt; 7) gut; 8) seaweed; 9) bacteria; 10) cancer

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