Gut microbes modify drugs

There is a saying that a drug is beneficial in one third of patients, ineffective in another third, and detrimental in the remaining third. This variability is partly due to genetic differences between individuals. A new study suggests that gut microbes play a big part as well: about two thirds of oral drugs may be chemically modified by gut microbes.

Zimmermann and coworkers found that two thirds of 271 oral drugs were metabolized by at least one of 76 bacterial strains that represent the majority of gut microbes. They identified 30 microbial enzymes that collectively converted 20 drugs to 59 candidate metabolites. These results complement previous observations that drugs influence the composition of the gut microbiome.

These finding should encourage the deep-pocketed pharma sector to put more efforts into elucidating the composition and role of the microbial communities hosted in our gut. If so, this could boost probiotics research as well.

Zimmermann et al. 2019 https://doi.org/10.1038/s41586-019-1291-3


ILSI and the funding of science

Early June 2019, I was surprised to see familiar names in the Dutch mainstream media. Not only the International Life Sciences Institute, but also the names of its founder and a former Executive Director of the Washington-based global center.

Less surprisingly, ILSI was being lambasted for being a scientific lobby group for the food industry. Never mind ILSI’s transparency about its funding and policies like having a Board majority of public trustees; for some people, all industry funding is suspect.

I do have a stake here. I’ve been Executive Director of ILSI Europe for nine years and was responsible for ILSI Europe’s scientific credibility from May 2003 until April 2012. I have never jeopardized it, nor have I ever been asked to let industry interests prevail over science.

Many years ago, when being criticized for taking industry money, I asked what source of funding of science would be acceptable. “Well, government money, of course” – what else would you expect UN staff to say?

There is not a single food company in the world that obliges me to buy their products, or forcefully separates me from my money. What does government do? They send me to jail if I don’t pay tax. They allocate part of my money to build things I appreciate like roads and (of even greater value, since I’m living below sea level) dikes. However, they also spend some of my money in ways that are scientifically unsound and in my view morally wrong, like subsidizing religion and overpopulation. So let’s not glorify government and their money.

Although most scientific publications are not influenced by their source of income, industry and government sporadically try to shape the conclusions of science they fund. This is wrong, and it can be prevented. Many safeguards are in place such as pre-registration of clinical trials. Moreover, peer review and the quest for reproducibility are strong forces ensuring that ultimately scientific truth will prevail, regardless of funding source.


The carbon fallacy    -    Cows are not cars   (pdf)

In discussions about climate change, all carbon emissions are seen as equally bad. It is saddening to observe that even a quality journal like Nature includes cattle-produced methane when calculating greenhouse gas emissions from food and comparing these to those of electrical appliances that are powered by fossil fuels.

Carbon released by livestock, mostly methane and carbon dioxide, is derived from plants. This “surface carbon” will be incorporated from the atmosphere back into plants and other photosynthetic organisms within days, years or centuries. However, the “deep carbon” released from oil, coal and gas by power plants and combustion engines will not be put back in its original form (buried deeply under earth's surface, inaccessible to the atmosphere) for millions of years.

Cycling of “surface carbon” by herbivores and plants has been part of life almost since its inception. Large ruminants, such as the bison herds roaming US prairies in the past, have been belching methane into the atmosphere for millions of years as part of the natural carbon cycle. This cycle has only been broken since humans started releasing “deep carbon” into the atmosphere by combusting fossil fuels. Capturing of anthropogenic carbon in million-year repositories will likely be required to decrease atmospheric carbon to pre-industrial levels.

Vandenbergh and Steensen Nielsen (2019) Nature Climate Change 9:8 https://doi.org/10.1038/s41558-018-0357-9

Camilleri et al. (2019) Nature Climate Change 9:53 https://doi.org/10.1038/s41558-018-0354-z


Potential breakthrough in crop yield and carbon capture

Photosynthesis is the key process enabling plant growth and life on earth. It is also a great way to capture carbon dioxide from the atmosphere into biomaterial. However, the efficiency of photosynthesis is limited by photorespiration, which helps plants to reduce the buildup of oxygen gas in their leaves without losing moisture.

South and colleagues engineered more efficient photorespiratory pathways into tobacco plants while inhibiting the native pathway. This increased photosynthetic efficiency and vegetative biomass by up to 40%. The authors are optimistic that similar engineering of crops may improve their yield, which would help nourish the increasing human population. They don’t mention it, but I would assume it would increase carbon capture by plants as well, helping to reduce the buildup of fossil fuel-derived carbon dioxide in the atmosphere.

South et al. (2019) Synthetic glycolate metabolism pathways stimulate crop growth and productivity in the field. Science 363:45. https://doi.org/10.1126/science.aat9077


Trouble brewing in our gut?

Researchers estimate that bacteria in the human intestine contain over 6000 genes that encode antimicrobial resistance (AMR). AMR is a health concern because it can make treatment with antibiotics ineffective.

The good news is, transfer of AMR genes from gut microbiota to pathogens is probably a very rare event. This makes sense. Antimicrobial resistance is a weapon in the never-ending war between bacteria, and it is good practice to stick to your guns rather than share them with others.

The bad news may appear to be the large number of antimicrobial resistance genes in our gut microbiota. However, initial results indicate that this is not the result of antibiotic use, as treatment of patients with antibiotics reduced the variety of AMR genes.

Antimicrobial resistance genes have been present for millions of years in the environment and may likewise have protected human gut microbiota from natural antibiotics long before we discovered penicillin. While we need to more deeply investigate gut-dwelling AMR genes to better understand the safeguards against their transmission to pathogens, at the moment I’m not losing sleep over them.

Ruppé et al. (2019) Prediction of the intestinal resistome by a threedimensional structure-based method. Nature Microbiol. 4:112. https://doi.org/10.1038/s41564-018-0292-6

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