Tien Sy Dong, MD, PhD, on Microbiome Changes After Bariatric Surgery in Patients With NAFLD

In this video, Tien Sy Dong, MD, PhD, discusses his research on how bariatric surgery can alter the microbiome of certain patients with fatty liver disease to accelerate weight loss.

Additional Resource:

• Dong TS. The microbiome changes induced by bariatric surgery protects against obesity and nonalcoholic fatty liver disease by decreasing gastric inhibitory protein and increasing hepatic NKT cell expression. Talk presented at: American Association for the Study of Liver Diseases: The Liver Meeting 2020; November 13-16, 2020; Virtual. https://thelivermeetingdigitalexperience.org/live-stream/19755551/Plenary-Basic-and-Translational-Discoveries 

Tien Sy Dong, MD, PhD, is an assistant professor in the Departments of Gastroenterology and Hepatology & Liver Transplantation at the University of California, Los Angeles. 

TRANSCRIPT:

Hello, my name is Dr Tien Dong. I am an assistant professor at the University of California Los Angeles in the Division of Digestive Diseases. I'm also a staff hepatologist here at the West Los Angeles VA. I am going to be giving you a quick, brief summary of my talk at AASLD this year.

The talk is entitled “The Microbiome Changes Induced by Bariatric Surgery Protects Against Obesity and Non‑Alcoholic Fatty Liver Disease: Decreasing Gastric‑Inhibitory Polypeptide and Increasing T Cell Expression.”

My research interest is focusing on how the microbiome plays a role in the development of obesity. As we all know, obesity has been this growing epidemic disease over the last several years. Despite everything we know about obesity, unfortunately, there's very few treatments for it.

The only good long‑term treatment so far that has been shown to have good beneficial effects for patients has been bariatric surgery. Over the last, I would say, 5 to 10 years or so, there has been a great deal of publication in regard to understanding how bariatric surgery can affect obesity.

What we found is that bariatric surgery, while it has changes in absorption of nutrients as well as changes in the GI tract, one of the major things that bariatric surgery also does is that it alters the microbiome in a very significant way.

In preliminary human studies, I would say, back in 2015 and 2017, published in Science, people have shown that if you took the microbiome of patients who underwent bariatric surgery and you transplanted that microbiome into germ‑free mice, the mice lost weight if the microbiome came from the patients after bariatric surgery.

That led down this pathway that the microbiome changes in bariatric surgery may be a contributing factor on how bariatric surgery induces weight loss. My research was to try to understand the mechanistic side of how that happens and why that happens.

In our study, what we did was that we took a cohort of patients that we were following who all underwent bariatric surgery. They were all female patients, and the total number was about 20 or so. Then we took their microbiome before they went to surgery, and then we looked at their microbiome 6 months after surgery.

What we found was that there was a group of patients who responded better to bariatric surgery than other groups. The microbiome at their baseline visit, before they underwent surgery, was highly predictive of if they were going to respond very well to bariatric surgery. Our definition of very well was losing at least 20% of body weight at 6 months.

What we saw in the human study was that there was this cohort of patients who had this very good microbiome at baseline that helped them lose even more weight with bariatric surgery. To try to get at the mechanistic side of things, what we did was, we then took these patients' microbiome, and we then transplanted them into antibiotic‑treated mice.

We took their microbiome before surgery and then after surgery. We put them into these mice, and then we gave these mice a high‑fat, high‑fructose, and high‑cholesterol diet, similar to a Western man. We also took these mice and also gave them a standard diet as well.

What we saw was that the microbiome was able to decrease obesity if it came from the microbiome of patients after bariatric surgery. The microbiome of patients after bariatric surgery lets you decrease adiposity, decrease fatty liver disease developments, decrease insulin resistance.

When we looked at the molecules that the microbiome was making, we saw that two things were happening. One was that the immune function of the liver was quite altered in the mice that had the microbiome of patients after bariatric surgery. These groups of microbiomes were able to alter the immune phenotype of the liver, causing them to have an increase in natural killer T cells.

What we also saw as well was that when we looked at the hormones of these mice, we saw that the microbiomes of patients after bariatric surgery led to a decrease in a specific polypeptide called gastric inhibitory polypeptide, or GIP.

The reason why this is interesting is because previous published papers have shown that the knockout of GIP was able to be protective against fatty liver disease, obesity, as well as diabetes.

What our studies have shown is that there's this deep connection between bariatric surgery and the microbiome and that the microbiome change induced by bariatric surgery is a very strong motivator on why patients lose weight.

Potentially, the ways that in which the microbiome does this is through alterations of GI hormones as well as alterations in the immune cells of the body. It's our hope that with future studies that maybe we can alter the microbiome of patients or target these pathways to help fight obesity and fatty liver disease.

With that, I would just like to thank you for listening to my talk.