Susceptibility and Resistance to Cholera Infection Can be Controlled by Varying the Gut Microbiome – Dr. Ansel Hsiao

Pharmacoengineering.comThis article was published on June 25, 2020

Cholera bacteria, TEM - Stock Image - C012/4990 - Science Photo ...
Figure 1. Scanning electron microscope image of Cholera.

People all over the world – healthy or not – can have the GI pathogen, Cholera (Figure 1), and their gut flora or biome can dictate whether they will be susceptible or resistant to the pathogen. This is also true of animals.

Dr. Salma Alavi (Ph.D. candidate –Figure 2; LinkedIn) is first author on this work of interest. Dr. Alavi has played a pivotal role to the success of this ground-breaking research. She works in the laboratory of Dr. Ansel Hsiao (Figure 3; google scholar profile), who is an assistant professor at the University of California at Riverside (UCR). He is part of the Institute for Integrative Genome Biology and the department of microbiology and plant pathology. His research group recently published an absolutely stellar article (Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection) in the highly prestigious journal, Cell. Cell has an impact factor of 36.2. This simply means that the average article published in the journal Cell will have approximately 36 citations after the first 3 years. Most researchers are happy when their article hits 10 citations, independent of the number of years it takes. That high of an impact factor is extremely rare, suggesting his research is highly thorough and meaningful. A graphical abstract is shown in Figure 4 but let’s dive into the details.

Profile photo of Salma Alavi
Figure 2. Dr. Salma Alavi – I also had the opportunity to ask Salma what her plans are next. She stated her plans are “to identify more novel pathogen-antagonistic microbes using the additional microbial subsets.” I look forward to seeing more of her successes in the future.

The 4 Main Takeaways

I had the opportunity to personally communicate with Dr. Hsiao and I asked him what the main takeaways are from the article. He said the following, and I quote:

1) Human microbiomes give widely varying resistance to infection by the human GI [gastrointestinal] pathogen Vibrio cholerae, the causative agent of the severe diarrhea cholera that affects millions of people annually worldwide.This variation is present in healthy US microbiomes as well as microbiomes based on those found in diarrhea and malnutrition-endemic areas, and suggests that inter-personal differences in microbiome can drive GI infection outcomes.”

To summarize this further, this means that people all over the world – healthy or not – can have the GI pathogen, cholera (Figure 1), and their gut flora or biome can dictate whether they will be susceptible or resistant to the pathogen. This is also true of animals.

Figure 3. Dr. Ansel Hsiao, University of California, Riverside.

2) Animals bearing defined microbiomes based on human gut communities in cholera endemic areas are highly susceptible to infection, and microbiome-dependent infection resistance can be restored through co-transplantation of healthy microbiomes into mice containing dysbiotic communities.”

3) An unbiased combinatorial approach using randomized microbiomes members identifies specific species that major contributors to colonization resistance that is durable in the presence of many different sets of gut microbes.”

4) Colonization resistance is mediated through the bile salt hydrolase enzyme activity of key microbiome members. This enzyme degrades the host molecule taurocholate that V. cholerae uses in the intestine to activate genes important for infection. The abundance of bile salt hydrolase genes in complete human microbiomes correlates to final infection outcome in animal models.”

Dr. Hsiao’s future research focuses on the following:

Figure 4. Graphical Abstract (Cell).

1) Elucidating the role played by quorum sensing in modulating the structure and function of the gut microbiota and virulence gene regulation in V. cholerae

2) Identifying mechanisms underlying gut microbiota-mediated colonization resistance against pathogens of the gut

3) Developing methods for manipulating the structure of the gut microbiota with a view to providing prophylaxis against bacterial enteropathogenesis

 

Alavi et al., Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection, Cell (2020), https://doi.org/10.1016/j.cell.2020.05.036

Pharmacoengineering.comThis article was published on June 25, 2020