Example of Microbiome Engineering Process: Gut Microbiome Engineering
In the last
post we discussed about Microbiome Engineering and Steps involved
In this
post lets understand the process with an example
Watch our Simple Summary You tube Video: What is Microbiome Engineering? Steps involved and Applications
What is
Microbiome engineering?
Definition:
Microbiome engineering is the purposeful
manipulation of microbial communities—through the addition, removal, or
modification of specific microbes, genes, or community structures—to confer
beneficial functions to hosts such as humans, animals, or plants.
Microbiome Engineering Procedure (with Gut
Microbiome Example)
Step 1: Define the engineering objective:
Identify the specific biological
function or therapeutic goal to be achieved by microbiome engineering (e.g.,
reducing inflammation, metabolizing toxic compounds).
In this example our
objective is to treat inflammatory bowel diseases through secretion of
anti-inflammatory cytokines by engineered Lactococcus lactis.
Escherichia coli and Lactococcus
lactis are common model gut bacteria isolated for engineering.
Step 2: Characterize the native microbiome:
Use multi-omics techniques
(metagenomics, metabolomics, transcriptomics) to analyze the composition and
function of the target microbiome ecosystem. This understanding is very
essential for achieving the objective.
Extensive study of host native microbiome, here it is human gut
microbiome using various methods.
Step 3: Isolate and select target microbes:
Culture or identify native gut
bacterial strains relevant to the engineering goal for modification.
Identify and Culture Lactococcus lactis native gut bacterial strains.
Step 4: Engineer microbes genetically:
Use suitable gene editing tools
(CRISPR, conjugation, electroporation) to add, delete, or modify genes that
confer desired functions such as therapeutic molecule production or metabolic
pathway alteration.
Genetically Engineer Lactococcus by
addition of genes for producing anti-inflammatory cytokines using any of the
suitable gene transfer or editing methods
Step 5: Design synthetic microbial consortia (optional):
Assemble multiple engineered
strains to create a community with synergistic or complementary functions if
applicable. This step is applicable if
many strains are microorganisms are used together.
Step 6: Ensure colonization and stability:
Optimize delivery methods and
ecological niches (e.g., providing selective nutrients) to promote persistence
of engineered microbes in the gut environment. The most challenging aspect of
microbiome engineering is the ability of engineered microbes to thrive in the
gut environment.
Simulate gut environment condition
in the culture, use specific dietary components (e.g., unique carbohydrates) or
engineered metabolic niches to ensure the engineered Lactococcus successful colonization and persistence in the gut.
Step 7: Test in model systems and optimize:
Evaluate the engineered
microbiome’s function, stability, and host interaction using animal models or
gut-on-chip systems; and improve design based on results.
Investigate how engineered Lactococcus
affect host physiology, immune response, and metabolism under controlled
conditions in animal models such as mice or rabbit.
Step 8: Clinical Trials in Host or Translate to clinical/real-world
application:
Conduct safety and efficacy
trials with engineered microbes in humans or target hosts, with continuous
monitoring of microbiome and health outcomes.
Conduct extensive safety and
efficacy trials with engineered Lactococcus in humans in reducing inflammatory bowel diseases via
secretion of anti-inflammatory cytokines, with continuous monitoring of
microbiome and health outcomes.
Learn Also: Topic 3 10 Applications of Microbiome Engineering
Reference
Arnold J, Glazier J, Mimee M.
Genetic Engineering of Resident Bacteria in the Gut Microbiome. J Bacteriol.
2023 Jul 25;205(7)
Albright, M.B.N., Louca, S.,
Winkler, D.E. et al. Solutions in microbiome engineering:
prioritizing barriers to organism establishment. ISME J 16,
331–338 (2022).
Bai, X., Huang, Z., Duraj-Thatte,
A. M., Ebert, M. P., Zhang, F., Burgermeister, E., ... & Zuo, T. (2023).
Engineering the gut microbiome. Nature Reviews Bioengineering, 1(9),
665-679.
Khan S, Hauptman R, Kelly L.
Engineering the Microbiome to Prevent Adverse Events: Challenges and
Opportunities. Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:159-179.