Obesity could increase severity of influenza study shows

By Dr. Ananya Mandal, MDMar 3 2020

A new study has revealed that those who are obese or overweight tend to get more severe bouts of influenza than those who are a healthy weight. The reason behind this could be the altered immune system of those who are obese. The study outlining this finding is published in the latest issue of the journal mBio from the American Society for Microbiology (ASM). The study was titled, "Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains."

Worldwide prevalence of obesity and overweight is nearly one in two say statistics. There has been a correlation between obesity and the severity of influenza. The team of researchers found that there is a diversity created in the virus among obese persons, and this could be one of the factors that cause a change in the influenza virus make up making it more virulent each year.

This was a preclinical study conducted on mice, and the alteration of the virus among obese lab mice was noted. The team states that among obese persons, there is a higher risk of severe influenza, and also, the levels of the virus emitted in the breaths of obese persons are found to be more significant. Obese and overweight persons also tend to have prolonged periods of shedding of the influenza virus. This study was conducted to explore the connection between obesity and influenza, the team explained.

However, lead author of the study Stacey Schultz-Cherry, Ph.D., a faculty member at St. Jude Children's Research Hospital and Deputy Director, World Health Organization Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds, explained, "We want to be careful about extrapolating too much from a mouse experiment, but the study does suggest that because of the problem with how cells respond to flu in an obese environment, individuals who are obese don't have good antiviral responses. They are delayed. They are blunted."

What was done?

The team performed their experiments on obese white mice and saw if the influenza viruses changed within obese mice. For this study, the team included two types of mice. One of the groups of mice was genetically obese called the "ob/ob mice (strain B6.Cg-Lep^ob/J)". These mice lacked a significant molecule called the leptin signaling molecule that regulated feeding behavior. Another group of mice was diet-induced obese mice called the DIO mice. These mice were infected with Influenza A virus, and the pathology and viral changes were noted.

Influenza flu virus illustration. Image Credit: Pinkeyes / Shutterstock

For this study, the team infected both lean and obese mice with influenza for three days and allowed the virus to multiply within their bodies. Viral samples were obtained from both lean and obese mice and reintroduced in obese and lean mice, respectively. Dr. Schultz-Cherry explained, "Basically, we wanted to mimic what would happen during an epidemic where the virus goes from one person to the next. What happens if a virus goes from a lean person to a lean person to a lean person versus an obese person to an obese person to an obese person."

The effect of the virus was also tested on "Obesity-derived normal human bronchial epithelial (NHBE) cells" to see if the findings held true in vitro as well.

Results

Major findings from the study show that some minor variants of the influenza virus emerged from the viruses infecting the obese mice. These minor variations then rapidly multiplied and were found to be more virulent than the usual strains. The team said that there was a decrease in type I interferon responses. The obese mice also responded late to the infection and thus in their bodies, the virulent strains of the virus emerged and grew. Mortality and pathology in the lungs also rose among obese mice found the researchers.

Dr. Schultz-Cherry, who is also a Chair of ASM's Public and Scientific Affairs Committee (PSAC), explained, "Obesity allows the virus to get in, replicate faster and make more mistakes. Some of those mistakes are potentially beneficial for the virus."

Implications and future directions

The researchers wrote that obesity increases the severity of influenza and this is due to the "altered microenvironment associated with obesity," They wrote that this led to, "the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts." They concluded that this change is "due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise."

Dr. Schultz-Cherry said some of the questions that remain were, "Do we see this increased viral diversity in obese people in what they are shedding? Is obesity part of why we now see so much viral drift each season, and why we have to continually update our vaccines?" As a next step, the researchers would explore these answers at a cellular level.