2016-08-01 15:42:32 UTC

Attendee Shares Experience from DDW® 2016 Active Learning Session on the Gut Microbiome

Aug. 2, 2016

Dr. Markham provides an overview of the AGA-American Gut Project session at Digestive Disease Week 2016 focusing on the gut microbiome.

By Nicholas O. Markham, MD, PhD, GI fellow, Vanderbilt University Medical Center. 

To see other reports from the AGA Active Learning Session on the Gut Microbiome at Digestive Disease Week® (DDW) 2016, check out the latest issue of The New Gastroenterologist.

Most of our patients suffer from diseases associated with altered gut microbiota. A special AGA Center for Gut Microbiome Research and Education session at DDW 2016 turned the table and presented microbiome data from AGA's own members and trainees. A panel of experts used data from members’ fecal samples to help define the state of microbiome science and provide evidence refuting the tongue-in-cheek hypothesis that gastroenterologists harbor the same bacterial alterations of those on the other end of the colonoscope.

In nearly all diseases, changes in gut microbial diversity are key. Fecal samples from patients with gastrointestinal diseases such as IBD, Clostridium difficile, obesity and many others, reproducibly contain a decreased richness in bacterial taxa compared to samples from healthy individuals.1 However, we do not fully understand the normal range of diversity within the healthy intestine. Several years ago, the Human Microbiome Project sought to clarify what "normal" means. Because of strict inclusion criteria, limited funding and few collection centers, the Human Microbiome Project comprised data mostly from young, healthy students. The American Gut Project, along with the British Gut Project, is the world's largest crowd-sourced citizen science project and has extended the Human Microbiome Project sample collection to all Americans regardless of age, health and socioeconomic status. It has raised over $1.1 million and sequenced over 10,000 samples. All data and analysis tools are open and free to the public.

At DDW, three of the field's top scientists led an active learning session to showcase the American Gut Project and present data from fecal samples submitted by AGA members. Dr. Lee Kaplan (Harvard University), Dr. Gary Wu (University of Pennsylvania) and Dr. Rob Knight (University of California, San Diego) each provided insights into our current understanding of microbiome science and technology.

In general, microbial diversity positively correlates with both age and sleep, but the most significant factor is diet.2,3 Eating a large variety of plants is associated with the greatest diversity of species in fecal samples. Other factors affecting diversity include IBD, season of collection, antibiotic exposure, sex, BMI, alcohol consumption and exercise.Other ways to modify the microbiome are active areas of research. The fecal microbiota transplant has been used successfully for recurrent Clostridium difficile infections and is showing promise for use in other diseases, like ulcerative colitis.5 Stanley Hazen's lab at The Cleveland Clinic has used small molecules targeting a specific gut bacterial enzyme that produces trimethylamine, which has been implicated in atherosclerosis.6 Dr. Wu summarized by noting, "This field is in its infancy, but already there are strong signals for future applications."

The primary objective of AGA in regard to the American Gut Project is to educate clinicians and scientists on the state-of-the-art techniques and analysis utilized in microbiome research. In doing so, the data helped satisfy a curiosity as to whether the microbiome of a gastroenterologist resembles that of his or her patients. Fifty samples were submitted by AGA members, which is about half the number of sample kits sent by the American Gut Project to AGA members who had volunteered to participate; a higher return rate than the general population. The protocols for processing and analysis were identical to those used by Gevers et al.7 Reassuringly, the represented microbes from AGA member samples were similar to the general population and did not segregate with IBD or Clostridium difficile patients.

With this project and nearly all microbiome analyses, there are limitations in sample collection and data interpretation. Many presentations during this year’s DDW echoed the difficulty with single sample collections. Such studies cannot reconcile the inherent day-to-day variability in fecal samples.3

Even with multiple samples over time, the relative abundance of specific bacterial taxa is merely correlative. We also do not yet understand the functional consequences of changing bacterial diversity. Like any new scientific field, characterization of the microbial components is critical and forms a foundation for functional and mechanistic studies. To that end, the American Gut Project is also studying samples of the skin, oral and vaginal microbiota. Dr. Knight offered the perspective that comparing organisms from these sites to gut microbiota would be like comparing bacteria from a coral reef to a Midwestern prairie. To further make his point, he showed a graph depicting the taxonomic distribution of our samples and reassuringly said: "Don't worry if you can't tell anything from that [figure], because nobody else can either. That's the state of the art."

Next year there may be an opportunity to include multiple samples per individual and to compare an individual’s samples from year to year. Also, the Knight lab has developed a high-throughput method for deeper sequencing analysis, namely shotgun metagenomics, to include the entire genetic contents of fecal samples, which will add an enormous amount of data to the existing 16S ribosomal DNA sequencing that has been used for bacterial species identification. These exciting expansions of the project will produce more longitudinal and functional data, including the whole genomes of all non-bacterial organisms (fungi, viruses, protozoa and archaea) present in the gut.

References
1. Tuddenham S., Sears CL. Curr Opin Infect Dis. 2015;28:464-470.
2. Wu GD., et al. Science. 2011;334:105-108. 
3. David LE., et al. Nature. 2014; 505:559-563.
4. http://americangut.org/wp-content/uploads/2016/02/mod1_main.pdf
5. Gupta S., et al. Ther Adv Gastroenerol. 2016;9:229-239.
6. Wang Z., et al. Cell. 2015; 163:1585-1595.
7. Gevers D., et al. Cell Host Microbe. 2014;15:382-392.

More on Clostridium difficile infection

How to Select the Best FMT Donor

Oct. 25, 2017

Dr. Gail Hecht debunks the myth that a patient’s family or friend is the best donor for a fecal microbiota transplantation.

Blog: Special 15th Anniversary Collection from Clinical Gastroenterology and Hepatology

Oct. 11, 2017

Celebrate this milestone with a look back at landmark articles, commentaries and reviews. Read more on the AGA Journals blog.

Study Finds C. Diff Infections on the Rise, FMT Most Promising Treatment

July 5, 2017

AGA is tracking outcomes of fecal microbiota transplantation through an observational registry.