A step toward 'living biotherapeutics'
Chemical engineers have created a coating for microbes that could make it easier to deploy the organisms to treat gastrointestinal disease

Date:
December 10, 2021
Source:
Massachusetts Institute of Technology
Summary:
Chemical engineers have developed a protective coating that helps
anaerobic microbes survive the manufacturing process, making it
potentially easier to use them to treat gastrointestinal disease.



FULL STORY ==========================================================================
The human gut is home to thousands of species of bacteria, and some of
those bacteria have the potential to treat a variety of gastrointestinal diseases.

Some species may help to combat colon cancer, while others could help
treat or prevent infections such as C. difficile.


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One of the obstacles to developing these "living biotherapeutics" is
that many of the species that could be beneficial are harmed by oxygen,
making it difficult to manufacture, store, and deliver them. MIT chemical engineers have now shown that they can protect those bacteria with a
coating that helps them to survive the manufacturing process.

In a study appearing today in the Journal of the American Chemical
Society, the researchers showed they could use the coating on a strain
of E. coli as well as another species that may aid in digestion of plant starches. The coating could be applied to many other species as well,
they say.

"We believe this coating could be used to protect pretty much any microbe
of interest," says Ariel Furst, the Raymond and Helen St. Laurent Career Development Professor of Chemical Engineering and the senior author of
the new study. "We think there are microbes out there that can help with
a variety of diseases, and that we can protect them for manufacture and production." MIT postdoc Gang Fan is the lead author of the study. Pris Wasuwanich, an MIT undergraduate, and Mariela Rodriguez-Otero, a former
MIT Materials Research Laboratory Summer Scholar, are also authors of
the paper.

Protective coating Most of the microbes that live in the human gut are anaerobic, and they have varying degrees of sensitivity to oxygen. Some
can tolerate a little bit of oxygen, while for others, oxygen is deadly.



==========================================================================
This makes it difficult to test their potential as treatments for human disease, because bacteria need to be freeze-dried and formulated as
capsules in order to be used therapeutically. In this study, Furst and
her colleagues decided to try protecting anaerobic bacteria by coating
them with a material made from metal ions and organic compounds called polyphenols.

When polyphenols and metal ions are put into a solution, they form a two- dimensional, grid-like sheet. For this study, the researchers used iron,
which is safe for human consumption, and three polyphenols that are all classified as GRAS (generally regarded as safe) by the Food and Drug Administration: gallic acid, tannic acid, and epigallocatechin (EGCG),
all of which are found in tea and other plant products.

If bacteria are also added to the solution, the material self-assembles
into a coating on individual bacterial cells. This coating protects
bacteria during the freeze-drying and manufacturing process. The
researchers showed that the coated cells were healthy and able to
perform normal cellular activities, although their growth was temporarily inhibited.

When exposed to an acidic environment, such as that of the stomach,
the coating breaks down and releases the bacteria.

Deploying bacteria One of the strains that the researchers used to
test the coating is Bacteroides thetaiotaomicron. This species, which
has enzymes specialized to digest carbohydrates, appears to be more
abundant in the gut microbiome of healthy people. However, it has been difficult to study how these bacteria might promote health if given as biotherapeutics, because they are very sensitive to oxygen.



========================================================================== Bacteria with this type of protective coating could also be useful
for agricultural applications such as helping to make crops more stress-tolerant.

Another possible application for the coating is to use it to protect
microbes that are used as vaccines. The BCG vaccine, which consists of
the bovine version of the microbe that causes tuberculosis, is difficult
to produce and must be stored at low temperatures. Coating it with a
protective layer could eliminate the need for cold storage and make distribution easier, Furst says.

"If we can remove the need for cold storage and transport, we think it
would make a lot of therapeutics more widely available," she says.

The research was funded by the MIT-Deshpande Center, the Undergraduate
Research Opportunities Program at MIT, and the MIT Materials Research Laboratory MRSEC Program of the National Science Foundation.

========================================================================== Story Source: Materials provided by
Massachusetts_Institute_of_Technology. Original written by Anne
Trafton. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Gang Fan, Pris Wasuwanich, Mariela R. Rodriguez-Otero, Ariel
L. Furst.

Protection of Anaerobic Microbes from Processing Stressors Using
Metal- Phenolic Networks. Journal of the American Chemical Society,
2021; DOI: 10.1021/jacs.1c09018 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211210093032.htm

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