rahma zakaria
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engineering the gut microbiome

For four types of interventions in the gut microbiome, describe what are the advantages or disadvantages of each approach.

Probiotics are bacteria that can be delivered to a host microbiome and alter then environment, such as by competing for nutrients, producing desired compounds, or affecting host immunity. For example, probiotics were used to deliver engineered E. coli producing NAPE, a lipid that can be converted to NAE to reduce food intake, to mice microbiomes for obesity reduction. Probiotics may provide opportunities for targeted microbiome modifications; however, it is difficult to predict how an introduced probiotic will actually act on the microbiome, and the effects might be transient or unexpected. Another challenge is that oral probiotic doses are orders of magnitude smaller than the trillions of organisms in the microbiota. (Sheth, 2016)
Fecal matter transplants involve engrafting microbiota from a healthy donor to a recipient. It has been used as last-resort treatments for C. difficile infection. By introducing a complete and stable community of gut microorganisms, the goal is to repair or replace the disrupted native microbiota. A challenge is that there isn't strong enough evidence to support fecal transplants as a rescue therapy. Randomized controlled trials haven't been conducted in North America because C. difficile outbreaks are sporadic and small, and it's difficult to obtain funding. (Boroda, 2012)
Bacteriophages/phages, or viruses that infect bacteria, provide a possible opportunity to modify microbial populations. Phages infect a microbe, reproduce using host machinery, and replicate, making them candidates for genetic engineering to selectively eliminate gut microbiome strains or transfer specific genes into microbial populations. While phages are beneficial because they're strain specific and can self-reproduce, a challenge falls in ensuring that delivered phage reaches the gut. Also, their effect may have a small magnitude. (Sheth, 2016)
Prebiotics are chemicals or nutrients that selectively promote growth or activity in a community. Prebiotics, such as nondigestible dietary polysaccharides, can be used to stimulate growth of commensal gut bacteria. However, it is difficult to rationally predict or change the specificity of their manipulations. (Sheth, 2016)

An overview of some methods of microbiome interventions. From Sheth, 2016


One future application of engineering the gut microbiome is human augmentation. Because the microbiome has been shown to have an impact on so many aspects of human health and development, (i) propose a type of human augmentation (e.g., extended alertness for sustained periods of time, reduced stress) and (ii) describe how a microbial intervention might produce that augmentation.

In my capstone class last semester, I became interested in thinking about the role of the microbiome in circadian rhythms, and considering whether engineering the microbiome could help in cases where a person's circadian rhythm is disrupted, such as in insomnia. It's an interesting problem because the gut has a circadian rhythm, and the brain has a circadian rhythm, and it's not known how the two circadian rhythms affect each other. Additionally, there is an internal circadian rhythm as well as a light-dark one. If there are neurotransmitters or small molecules that play a role in modulating circadian rhythm, perhaps an engineered microbe could be delivered to the gut containing a circuit that expresses or processes such molecules at a particular programmed pattern.

learning about our microbiome


Culturing bacteria from our hands and mouth.

We chose one of the colonies growing on the plate to submit for sequencing. When we received the results, we used BLAST local alignment search to identify the strains.

The colony I chose from my oral microbiome plate had highest identity to either Staphylococcus aureus or Staphylococcus haemolyticus. Staphylococcus species are found on a moderate percentage of oral microbiomes.

A study of the microbiome composition of 120 individuals. Image from Hernandez, B. Y., Zhu, X., Goodman, M. T., Gatewood, R., Mendiola, P., Quinata, K., & Paulino, Y. C. (2017). Betel nut chewing, oral premalignant lesions, and the oral microbiome. PloS one, 12(2), e0172196.

The colony from the hand microbiome was identified as Kocuria rhizophila, a soil dwelling Gram-positive bacterium which is also used industrially for antimicrobial testing and in food preparation.

tape-based microfluidics


We made a microfluidic device with laser-cut tape, a PDMS layer, a glass slide, a cover slip, and some tubing. We flowed bacteria cultures through the device and tried to view bacteria under the microscope.