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Microbiota Alterations In Obesity And Sister Complications

In my previous blog post, I briefly discussed the importance of microbiome research and how to take the first steps in conducting a microbiome study. In today’s post, I will continue to discuss the importance of this area of research with a focus on obesity.

The worldwide epidemic of metabolic syndrome and obesity in different age groups both in the United States and around the world is considered as a major public health concern. Moreover, the human gut microbiome has been linked to metabolic disease and adiposity and it is not only a marker of disease, but also contributes to pathology.

Intestinal microbiota plays a critical role in the host metabolism and immune system that extents its related physiological functions to other organs including brains, liver and adipose tissue. Metagenomic-wide association studies indicate significant changes between gut microbiota metagenome of metabolically healthy versus unhealthy individuals. Such microbiota changes are thought to be a possible cause of obesity and therefore, intestinal microbiota represents a potential therapeutic target to manage obesity.

Overview of gut microbiota role in host metabolism

Overview of gut microbiota role in host metabolism. The shift in gut bacteria can affect host metabolism via several pathways in different tissues.

Study results have illustrated alterations in the dominant gut phyla of obese subjects/animals, reporting significant reduction in Bacteroidetes and significant increase in Firmicuts and Actinobacteria. The consequence of this shift in gut microbiota is the increased potential of harvesting energy from food and a low-level inflammation. Obesity leads to a low level inflammation, specifically in adipose tissue, that results in the production of several inflammatory cytokines, which may lead to insulin resistance as well. TNF-α, IL-1β and CCL2/MCP1 are among the important inflammatory cytokines that are induced in obese state accompanied by increased macrophages, T cells and mast cells. Presence of the aforementioned cells not only correlates with the gene expressions that control inflammation, but also indicates the possible role of innate immunity in obesity and insulin resistance. Moreover, Pattern recognition receptors such as Toll-like receptors (TRLs) are activated by bacterial endotoxins such as lipopolysaccharide (LPS), which results in innate immune response and inflammation. Also, gut microbiota produce wide range of molecules, such as flagellins and peptidoglycans, which activate inflammatory pathways leading to obesity and insulin resistance. Recent data from mice genetically deficient in TLR5 reported significant changes in their microbiota and development of metabolic syndrome characteristics. Results from germ free mice also illustrated possible effects of gut microbiota on host metabolism. High fat – high sugar diet fed mice did not show same metabolic disturbance in comparison with not germ free littermates. Microbiota transplantation from obese mice also resulted in greater adiposity in comparison with lean donor recipients. It is also suggested that short chain fatty acids (SCFAs) may contribute to regulation of gut dysbiosis. These compounds such as butyrate, acetate and propionate are produced by intestinal microbiota as a result of diet-derived fibers fermentation. SCFAs are thought to be the energy source for intestinal epithelium and liver, whereas they can also play a modulatory role in immune response via reducing gut permeability.

Shayan Mohammad Moradi Headshot

Shayan is a caffeine-dependent Ph.D. Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).

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A Short Look Into How To Conduct A Microbiome Study

Lines of evidence and range of conditions with host-microbiome interactions continue to rise. Therefore, many researchers from various fields are interested to see whether gut microbiota or its related metabolites are associated with pathologies and whether targeting specific microbes or microbial metabolites can show novel therapeutic properties. So, it is critical to understand different aspects of microbiome studies for “first” microbiome projects. In general, microbiome data are majorly obtained by three approaches: Metagenomics (which bacteria are present), Metatranscriptomics (which bacteria have active gene expression) and Metabolomics (which bacterial metabolites are present) (Figure).

metagenomics, metaranscriptomics, and metabolodics diagram

Major approaches for obtaining microbiome data: Different approaches aim to investigate different outcomes yet, a combination of various methods would result in a better understanding of microbiome with respect to different disease phenotype.

Sequencing of metagenome allows portraying of functional potentials and is based on the direct sequencing of total DNA. This approach allows the investigation of gut microbiota composition and usually involves next generation sequencing after extracting sample DNAs. A widely used and popular economical method is 16s rRNA gene surveys, which can be scaled to larger projects. 16s rRNA gene is a housekeeping genetic marker that is highly conserved between different species of bacteria. Also, these 16s rRNAs contain hypervariable regions that are bacterium specific; hence, it will allow identifying and quantifying different bacterial taxa within the gut microbiome samples.

Based on the specificity of different types of enzymatic machinery, the gut microbial composition and activity may be characterized by the profile of small metabolites that are produced in the gut.  The advent of omics-based system biology has provided novel opportunities for deciphering the gut ecosystem and its interplay with body metabolism and the role of nutrients in health as well as the cross talk of distinct factors in disease development. In other words, gut metabolites comprise a plethora of derivatives of the intermediate metabolism that can be explored by metabolomics approaches in a more exhaustive fashion to discriminate between healthy and unhealthy subjects.

Regardless of the approach taken to study gut microbiome, many of the fundamentals are shared between different methods. The challenge would be to interpret the human body as a single system rather than single parts, therefore, a range of approaches should be used to analyze the metabolic interaction of host and gut microbiota. Hence, combining different approaches backed up by rigorous statistical assessments may generate a holistic view of the metabolic interactions between gut microbiota and whole body.

Shayan Mohammad Moradi Headshot

Shayan is a caffeine-dependent Ph.D. Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).

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Are You New To AHA Conferences? Lessons From 2017 Scientific Session

AHA Sessions

“No grand idea was ever born in a conference, but a lot of foolish ideas have died there.”
F. Scott Fitzgerald

As a researcher mostly involved in basic science, you may have numerous ideas that you think are worth pursuing, until you join your peers’ conversation in a conference and then, you realize, that may have been a foolish idea to pursue, precisely as Fitzgerald said.  This is only one beauty of attending conferences and for me, my recent experience at #AHA17 made me to wholeheartedly believe in Fitzgerald’s saying.
 
I attended this year’s Scientific Session with two mindsets:

  • First, I tried to have a pre-made mindset about the topics I would like to follow-up on (aortic aneurysms, atherosclerosis, and lipid metabolism).
  • Second, I kept a portion of my mind empty and looked for ideas to fill it up with.

By focusing on a specific topic, I was able to explore different projects which were to some extent, related to what I do, I shook hands with many researchers who are active in my field, I had the chance of establishing connections with potential future collaborators, and finally based on all the talks and communications, I killed some foolish ideas. None of these would have been possible without a planned attendance and pre-made mindset

Keeping a blank space in my mind helped me to look for fillers. From getting myself exposed to projects presented in other AHA Councils, to having snacks with scientists who have opposite ideas, the fruitfulness of activities which are usually out of my field of focus not only gave me new ideas to work on but also expanded my networking circle to an extent which I would not expect.

All things considered, #AHA17 was the highlight of my conference participations in 2017 and if you are planning for your next AHA conference attendance, do not forget to come prepared with an open mind to get the most out of the event(s).
Also, as a blogger in the events, it’s best to avoid beer. Sometimes that first draft can get in the way of your novel ideas.

Shayan Mohammad Moradi Headshot

Shayan is a caffeine-dependent Ph.D. Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).

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Improving Scientific Presentations: Lesson 1

man in front of audience

American Heart Association Annual Scientific Session consists of hundreds of talks from a wide range of presenters including students, post-doctoral scholars, and faculties at different levels. Seating in various #AHA17 sessions makes me think about what William Yeats, one of the foremost figures of 20th-century literature, said years ago:

“I always think great speakers convince us not by force of reasoning but because they are visibly enjoying the beliefs they want us to accept.”

I still believe that this is one of the most important fundamental points to successfully convey your scientific message; what you will not always see in scientific presentations. So let’s discuss basic points of executing a good talk by tackling the most common problem: Podium Panic. In order to overcome this problem, I like to do the “4 Ps” method – Plan, Prepare, Practice, and Perform.

To plan, make sure you know your audience and the range of their knowledge and why you are talking to them. Is it a summary of your progress to your advisory committee or it is a special seminar to prove your concept. The answer to these questions helps you to form your story.

To prepare, study what you have to study, make ready your handouts (if there are any) and start working on your slides. Do not have “sliduments”, slides that look like documents. 

To practice, make sure to find at least one person to listen to your talk and do not forget to get feedback. Another crucial point is NOT to memorize your talk, rather learn what you will discuss. The latter helps significantly to reduce stress.

To perform, when you planned, got prepared and practiced; now you can just go on the stage and perform. Do not forget to show everyone how excited you are about what you are talking about. 

Shayan Mohammad Moradi Headshot

Shayan is a caffeine-dependent Ph.D. Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).

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When One Teaches, Two Learn: Core Values Of Mentor/Mentee Relationship

laptop, glasses, and paper working late into the night

Whether you are a junior graduate student or an established faculty, there is always something that you can learn. Whether you want to write your very first pre-doctoral fellowship grant or learn how to tweet about your center’s accomplishments, there is always someone that you can count on as your guide. That was the first point that stood up to me when I arrived at the 2017 Scientific Sessions. As the days went by, I started to appreciate the sacred bond that we AHA17 attendees all share: We are all mentees. Despite this mentality, young mentees point of views are often ignored. The ignorance is often derived by cultural differences, generation gaps and unbalanced expectation levels which may exist in the environment that the mentee is growing. To tackle this issue, having core values that helps flourishing the mentor/mentee relationship seems to be crucial. Therefore, as a young mentee and based on what I learned throughout the sessions in the meeting, I propose the following fundamental points to be considered as an infrastructure for establishing a successful mentor/mentee relationship:

  1. Find a synergy between your past experiences and the training opportunities in the new environment.
  2. Clarify your expectations from your mentor/mentee.
  3. Have short-term and long-term plans.
  4. Have self-assessments of your success in accomplishing your goals
  5. Either as the boss or the student, do not expect wins from the other party. Loosing is learning.
  6. Do not hide. Do not be an investigator who is just a name on papers and do not be a student who no one knows.

Having such major core values helps the establishment of relationships that will last for a long time and help both sides to move forward. As Phil Collins beautifully said years ago, “In learning you will teach and in teaching you will learn.” So, no matter which stage you are at, respecting the aforementioned points can help to be both a better learner and a better teacher at the same time. 

Shayan Mohammad Moradi Headshot

Shayan is a caffeine dependent PhD Candidate at the Saha Cardiovascular Research Center, University of Kentucky. His research area is focused on vascular biology and lipid metabolism. He tweets @MoradiShayan, blogs at shayanmoradi.com and he is the Winner of World’s Best Husband Award (Category: nagging).