Solving obesity: Could manipulating microbes offer an alternative to weight loss surgery?

March 13, 2020

Already considered a global epidemic, human obesity continues to be on the rise. According to the Centers for Disease Control, more than 40% of the U.S. population is considered obese.

The gamut of adverse health effects associated with obesity is broad, including such devastating illnesses as Type 2 diabetes, coronary artery disease, stroke, sleep apnea and certain forms of cancer. Patients often suffer depression, loss of mobility, social isolation and inability to work. As a doctoral student in Rosa Krajmalnik-Brown’s laboratory, Zehra Esra Ilhan led a recently published study that advances our understanding of how gastric bypass surgery affects the gut microbiome. Ilhan is currently conducting research at INRAE-French National Institute for Agriculture, Food and Environment. Download Full Image

With costs approaching $316 billion dollars annually in the U.S., understanding how to quell obesity will result not only in a healthier population, but could also help reduce runaway medical costs.

Despite the looming need to address obesity, the causes are not well understood. Researchers generally agree that genetic and gut microbiome composition and activity are important factors in determining who is obese and who isn’t.

As interest and understanding of the human microbiome increases, researchers are increasingly looking to the gut for answers that can lead to new, more effective diagnostics and therapies.

The trillions of microbes in the human gut perform a vast range of critical functions in the body and have even been implicated in mood and behavior. Among microbes’ critical responsibilities are the micromanagement of nutrients in the food we digest — one of the reasons for their central role in the regulation of body weight.

In a new study, "Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery," recently published in NPJ Biofilms and Microbiomes, ASU researcher Zehra Esra Ilhan, ASU Biodesign Professor Rosa Krajmalnik-Brown and researchers from Mayo Clinic and Pacific Northwest National Laboratory have taken another step in understanding how the gut changes after gastric bypass surgery (also known as Roux-en-Y gastric bypass surgery).

“Our findings highlight the importance of changes in mucosal and fecal microbiomes that are reflected on gut metabolism after surgery,” Ilhan said. "The microbial changes after surgery corresponded to persistent changes in fecal fermentation and bile acid metabolism, both of which are associated with improved metabolic outcomes.”

portrait of Rosa Krajmalnik-Brown

Rosa Krajmalnik-Brown is a professor in the ASU School of Sustainable Engineering and Built Environment and faculty in the School of Life Sciences. At the Biodesign Institute, she practices as part of the Swette Center for Environmental Biotechnology.

In addition to the expected weight reduction and improvement in obesity-related comorbidities after gastric bypass surgery, the researchers observed that the impact of surgery is not limited to fecal communities; mucosal communities are altered as well. Changes in the microbiome were linked to increased concentrations of branched-chain fatty acids (amino acid fermentation products) and an overall decrease in primary and secondary bile acid concentrations in fecal samples. Bile is an alkaline fluid that aids digestion.

“Previous bariatric surgery-microbiome studies in humans relied largely on fecal samples because sampling through the intestinal mucosal membrane requires an invasive procedure,” said Ilhan, lead researcher for the study. At the time of the study, Ilhan was a doctoral student in Krajmalnik-Brown’s lab. She is currently conducting research at INRAE-French National Institute for Agriculture, Food and Environment.

Bariatric surgery is an operation that causes people to lose weight by making changes to the digestive system. These changes are physiological and chemical and include gastric restriction, malabsorption, bile acid metabolism and chemical signaling.

“The mucus membrane is a critically important site for host-microbe interactions. We understood that with fecal sampling, we had an underrepresented picture of how the mucosal communities actively interact with host immune system and epithelial cells,” Ilhan said. (Epithelial cells are cells that line the surfaces of your body.)

Although gastric bypass surgery has been successful for many patients suffering from morbid obesity, it is a serious, invasive procedure that is not without risk and expense. In addition, some patients regain the weight they have lost, perhaps because they lack the favorable microbes necessary for permanent weight loss.

“Understanding the microbial behavior in the gut could potentially lead to a creating a probiotic that could replace surgery – or an improved indicator to identify the best candidates for surgery and sustained weight loss," Krajmalnik-Brown said. 

An illustration of the cross-section of a healthy colon with its microbiota. The outer mucus layer and the colon lumen are colonized by different microbiota and therefore, produce different metabolic end products. Figure from “Microbiome After Bariatric Surgery and Microbial Insights into Surgical Weight Loss, A Dissertation Presented in Partial Fulfillment of the Requirements for the Degree: Doctor of Philosophy” by  Zehra Esra Ilhan

In the longitudinal study, subjects provided fecal samples and rectal mucosal samples. The rectal mucosal samples were collected via un-sedated flexible sigmoidoscopy at baseline, and again at 12 months post-gastric bypass surgery. Researchers analyzed microbial DNA that was extracted from the fecal and mucosal samples. Fecal metabolites were analyzed using high-throughput metabolomics approaches.

A tell-tale indicator of pathology in obese patients has been found in the gut, where a markedly lower diversity of microbial communities is observed. A high diversity of gut microbes is essential to good health.

In 2009, Krajmalnik-Brown’s research team showed for the first time that gastric bypass surgery produced profound changes in the composition of microbial communities in the gut. The gut flora of postsurgical gastric bypass patients showed a marked difference from obese and normal weight patients.

In a 2017 study, the team took another step by comparing how microbes and the metabolome (the metabolome is the total number of metabolites present within an organism, cell or tissue) change after gastric bypass surgery and lap band surgery.   

The 2017 study demonstrated that gastric bypass surgery caused a dramatic reorganization of the gut, which increases microbial diversity. Changes in the gut microbiota related to lap band surgery (also known as laparoscopic adjustable gastric banding) were mild and accompanying weight loss was less pronounced. Earlier studies have demonstrated that fat is reduced and weight loss triggered when germ-free mice receive a fecal transplant from mice who had undergone gastric bypass surgery. 

Krajmalnik-Brown’s team is currently working on a project funded by the National Institutes of Health in which the main goal is to quantify the contribution of the microbiome to the host energy balance. This project is intended to move the field from associations to causality and help identify how microbes and metabolites can fight obesity.

Krajmalnik-Brown is a professor in the ASU School of Sustainable Engineering and Built Environment  and faculty in the School of Life Sciences. At the Biodesign Institute, she practices as part of the Swette Center for Environmental Biotechnology.

Krajmalnik-Brown is also known for her research into the role of the microbiome in those with autistic spectrum disorder.

Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK090379

Written by Dianne Price, Biodesign Institute

Charitable giving times four

Four siblings, who are also ASU Barrett grads, establish scholarship for honors students

March 16, 2020

Four siblings who graduated Arizona State University with distinction from Barrett, The Honors College have created a scholarship to give back to the community that gave so much to them.

Brett, Chase, Scott and Jenna Fitzgerald recently established the Fitzgerald Scholarship with an initial $25,000 endowment. Scott Jenna Brett Chase Fitzgerald Scott, Jenna, Chase and Brett Fitzgerald have established the Fitzgerald Scholarship to benefit students in Barrett, The Honors College at Arizona State University. Download Full Image

“Barrett gave my siblings and me a platform to succeed. We thought it was only right to give back to the school that gave us so much,” Scott said.

Chase echoed his brother’s thoughts: “Barrett has enabled my entire family to find fast and frequent success in our careers and we thought it fitting to, in turn, start paying back early and often.” 

The common threads that bind the Fitzgerald siblings are high academic achievement, leadership in community service, competitive professional endeavors and an interest in study abroad.

Brett graduated in 2013 with concurrent bachelor’s degrees in finance and legal studies and an international business certificate. He was a Fulbright English teaching assistant in South Korea and a Tillman Scholar. While at Barrett, he studied abroad each summer, visiting Costa Rica, Peru and Ecuador. Additionally, he was a Barrett Honors Devils member and Barrett Mentor. He currently works as an account executive for Mulesoft, a Salesforce company, in Chicago.

Chase graduated in 2015 with a bachelor’s degree in biological and biomedical sciences. He was a Fulbright English teaching assistant in South Korea and a Tillman Scholar. During his junior year, he created Page Turners, a Barrett student organization that helps elementary school children develop reading skills. He also was a Barrett Ambassador, Barrett Honors Devils member and a Barrett Mentor. He participated in a China study abroad program and a clean water project in Honduras. This spring, he will graduate from the University of Arizona College of Medicine in Phoenix.

Scott graduated ASU in 2018 with bachelor’s degrees in finance and business data analytics. He was a Tillman Scholar, a Page Turners reader and a W. P. Carey School of Business office intern. He now works in information technology consulting with KPMG, a global professional services and accounting firm.

Jenna graduated in 2019 with concurrent bachelor’s degrees in marketing and psychology. She was a Tillman Scholar, an ASU Track and Field pole vaulter, a Barrett Ambassador, a W. P. Carey facilitator, ASU first year success coach and W. P. Carey office intern. She currently works in recruiting for Deloitte, a global accounting and professional services organization.

The Fitzgerald Scholarship is to support top honor students with financial need and an interest in national scholarships.

The Fitzgeralds prefer that scholarship recipients plan to apply through the Lorraine W. Frank Office of National Scholarship Advisement for a nationally-competed scholarship including Fulbright, Boren, Marshall, Rhodes and Truman.

In addition to scholarship funds, the Fitzgeralds will offer professional mentoring to recipients.

“We hope to support Barrett students and help them achieve their amazing potential, just like our mentors have done for us,” Jenna said.

We caught up with the Fitzgeralds to get their thoughts about Barrett, their fondest memories of the honors college and how their honors experience helped them get to where they are now. Here’s what they had to say:

Question: What drew you all to ASU and Barrett?

Scott: Deciding on Barrett and ASU was a no-brainer. Given that I wanted to stay in-state for my college education there was really only ever one option. Barrett provided a liberal arts college feel with the shared resources of a large public university. Having two brothers already build their own legacies at ASU, there was never a doubt in my mind on where I wanted to attend school.

Jenna: Witnessing how happy and successful my three older brothers were at ASU opened my eyes to all the amazing opportunities that come with such an inclusive, well-supported university. In addition, pairing that large university feeling with the intimate community Barrett fosters, I knew it was the right place for me too.

Q: What are your favorite memories from Barrett?

Chase: Living and developing a community as an on-campus Barrett student set me up for much of my academic and extracurricular successes, which were all proud experiences. However, my most fond memories come from the pride and support my Barrett friends and I were able to contribute to our sports teams, including one time where we found ourselves camping for tickets outside Wells Fargo Arena while studying and taking our first semester’s final exams.

Brett: My favorite memories from Barrett were developing my thesis with Pat Tillman Scholarship Program classmates, as well as study abroad trips with Professor (Ted) Humphrey and Associate Dean (Janet) Burke to Costa Rica, Peru and Ecuador!

Q: What was the most resourceful tool you utilized at Barrett?

Jenna: The community, hands down. Barrett selects such awesome community assistants (CAs) that live alongside freshman students and mentor them throughout their time at ASU. By integrating myself among them — some of the smartest, most compassionate individuals — I was able to discover a sense of self-worth and a worldly perspective that serves me to this day.

Scott: The Barrett dining hall will always hold a special place in my heart, but I think the most beneficial tool is the academic advisers. Cindy Patino was someone who I could go to for anything, whether it was concerns over my schedule or struggles in my personal life. Cindy provided me with continuous support throughout my college career.

Q: How did Barrett prepare you for life after college?

Brett: Barrett taught me how to think critically, balance a heavy workload and interact with students from all majors and backgrounds. The experience I had at Barrett and ASU has served as a microcosm of life and therefore, I’ve been able to take my learnings and be a successful Fulbright ETA and tech salesman postgraduation.

Chase: Barrett challenged me to embrace academic rigor as a tool for self-empowerment. My time living within the academic community also reinforced my beliefs of the importance of collaboration and intentional action and seeking out highly motivated people with disparate interests in order to bring fresh ideas to the table.

To learn more about how to apply for national scholarships, visit the Office of National Scholarship Advising website.

Nicole Greason

Public relations and publicity manager , Barrett, The Honors College