Breaking Down Methionine as an Alternative to a Low Methionine Diet
In animal studies, reduced intake of the essential amino acid methionine mimics many of the beneficial effects of calorie restriction on long-term health and life span, even when calorie intake is maintained at the same level as the control groups. One of the triggers for the calorie restriction response to increase cell maintenance activities is based on nutrient sensing that is specific to methionine. Low methionine diets are perhaps more challenging to organize than the practice of calorie restriction, however. Researchers here offer an interesting alternative, which is to use an enzyme to break down methionine in the diet before it has the chance to enter the body. That enzyme can be delivered directly in the diet or, intriguingly, manufactured by bacteria that are introduced to the gut microbiome.
Obesity increases with aging. Methionine restriction affects lipid metabolism and can prevent obesity in mice. In the present study we observed C57BL/6 mice to double their body weight from 4 to 48 weeks of age and become obese. We evaluated the efficacy of oral administration of recombinant-methioninase (rMETase)-producing E. coli (E. coli JM109-rMETase) or a methionine-deficient diet to reverse old-age-induced obesity in C57BL/6 mice.
Fifteen C57BL/6 male mice aged 12-18 months with old-age-induced obesity were divided into three groups. Group 1 was given a normal diet supplemented with non-recombinant E. coli JM109 cells orally by gavage twice daily; Group 2 was given a normal diet supplemented with recombinant E. coli JM109-rMETase cells by gavage twice daily; and Group 3 was given a methionine-deficient diet without treatment.
The administration of E. coli JM109-rMETase or a methionine-deficient diet reduced the blood methionine level and reversed old-age-induced obesity with significant weight loss by 14 days. There was a negative correlation between methionine levels and negative body weight change. Although the degree of efficacy was higher in the methionine-deficient diet group than in the E. coli JM109-rMETase group, the present findings suggested that oral administration of E. coli JM109-rMETase, as well as a methionine-deficient diet, are effective in reversing old-age-induced obesity. In conclusion, the present study provides evidence that restricting methionine by either a low-methionine diet or E. coli JM109-rMETase has clinical potential to treat old-age-induced obesity.
It could certainly be cheaper for people to take a daily or weekly probiotic shot of genetically engineered E. coli bacteria, rahter than one of the new and expensive (without insurance) weekly "skinny jabs".
Given that Type 2 diabetes already costs the NHS here in the UK around 10 billion pounds a year, it would be good for society as a whole. But I suppose regulatory barriers will prevent this?
Genetically modifying bacteria seems to be within the capbabilities of biohackers. I wonder if any could reproduce these bacteria and then sell them via the internet?
Pretty cool! Is there a significant advantage to ingesting the genetically-engineered bacteria, rather than just the enzyme, though? Seems like an unnecessarily expensive (and risky) step otherwise.
This is an earlier paper from some of the same group, where the mice just ingested the enzyme: "Oral Recombinant Methioninase Prevents Obesity in Mice on a High-fat Diet"
https://iv.iiarjournals.org/content/34/2/489