A new therapy involving engineered gut bacteria may help reduce certain health problems associated with obesity.
This method is based on incorporation of specially-engineered bacteria into the intestines of mice and which subsequently protect the mice from gaining weight and against some of the negative health effects of obesity.
There is accumulating evidence that gut microbiota may play a critical role in obesity and hence, may offer a new therapeutic target. The aim of the study by Dosoky and colleagues was to determine whether obesity-related diseases might be treated or even prevented by altering the gut microbiota. Gut bacteria were manipulated to produce a small lipid molecule to aid suppression of appetite and reduction of inflammation. People who are obese do not produce enough of this lipid, which is made in the small intestine.
The principle of using engineered bacteria to inhibit obesity was previously demonstrated in standard mice which were fed a high-fat diet. This study was done in mice which were prone to develop atherosclerosis and fatty liver disease, and the results showed that the engineered bacteria were beneficial not only in suppressing obesity, but also in protecting against fatty liver disease and atherosclerosis.
Mice fed a high-fat diet whilst simultaneously receiving the engineered bacteria via drinking water exhibited less body weight gain and body fat, in contrast to mice given standard drinking water or control bacteria. Engineered bacteria were also administered to mice with increased susceptibility to atherosclerosis and fatty liver disease. The mice which received the engineered bacteria accumulated less fat in the liver and showed reduced expression of markers of liver fibrosis, compared to mice that did not receive the treatment. The treated mice also exhibited a modest trend toward reduced atherosclerotic plaques.
Results of this work indicate that it might become possible in future to treat the negative effects of obesity by administering these bacteria to man. Overall, it is becoming very compelling that the little guys in the human gut may actually represent tiny organs serving specific and essential physiological functions. Obesity is now regarded as a metabolic disease, and not as a consequence of unhealthy lifestyle as it used to be historically. It is time that people who suffer from obesity are not incriminated and discriminated against. It is thought that up to 40% of the adult population in Mauritius are overweight or obese, with severe impact on their health and quality of life. Body weight is a major risk factor for type 2 diabetes. The most successful treatment for obesity is weight-loss (bariatric) surgery, which is proving to be quite popular in several countries. The surgery is also associated with a compelling phenomenon whereby it also leads to remission of type 2 diabetes. However, ultimately bariatric surgery is invasive, carries some risk, is expensive and not necessarily suitable for every obese patient with diabetes. Thus, a surgery-free alternative is preferred. Several recent studies from Dr Ramracheya’s laboratory in Oxford have demonstrated that reversal of diabetes could be achieved without the need for bariatric surgery (Ramracheya et al., 2016; Guida et al., 2018, 2019).
Author: Dr Reshma Ramracheya is a group leader at the University of Oxford with over 18 years of experience in teaching and medical research.
Reference:
Dosoky NS, Guo L, Chen Z, Feigley AV, Davies SS. Dietary Fatty Acids Control the Species of N-Acyl-Phosphatidylethanolamines Synthesized by Therapeutically Modified Bacteria in the Intestinal Tract. ACS Infect Dis. 2018 Jan 12;4(1):3-13. doi: 10.1021/acsinfecdis.7b00127. Epub 2017 Oct 17
