One of the better known health facts is that cigarette smoking is bad for you. Unsurprisingly as in the USA it kills nearly half a million people a year and globally tobacco kills more than 8 million people each year — about half of its users.
So people, why don’t you just give it up? Well, part of the problem is that nicotine is a highly addictive chemical — it’s an alkaloid produced by the nightshade family of plants — and addiction means that habitual users crave the stuff itself and also desire its effects. And there’s a behavioural factor — a dependence on tobacco in certain situations, e.g., after meals or when feeling stressed. But that’s not all: there’s convincing evidence that, as a result of nicotine’s appetite-suppressing effects, weight gain is a common side effect of quitting — to the tune of between 5 and 10 kilograms in the year after stopping. Mmm.
Clues about weight gain
Over the last few years odd reports have appeared showing that stopping smoking can really upset the human gut microbiota — the population of microorganisms (mainly bacteria) that live in the intestine. It’s an effect called dysbiosis (or dysbacteriosis) — an imbalance in the microflora that changes how they affect metabolism. Probably no surprise to readers of these pages as what I’ve called our ‘secret army’ — the bugs that share our body to the extent that these little guys outnumber us on a cell-to-cell basis — have popped up with increasing frequency in the context of cancer (Bugged!, Our Inner Self, Secret Army: More Manoeuvres Revealed, it’s a small world).
To get at the problem of getting bigger after quitting (aka smoking-cessation-induced weight gain, SCWG), Leviel Fluhr and colleagues at the Weizmann Institute of Science, Rehovot, Israel noted these earlier results and set up mouse models to look in detail at what happens in the guts of mice (impersonating humans) when they stop smoking (i.e. they’re removed from a whole-body smoke exposure chamber).
First they showed that mice exposed to smoke for 21 days gained weight after cessation (about 10% over 20 days) — mimicking the effect seen in humans. Then they showed that a combination of four antibiotics significantly reduced weight gain, a smoking gun as you might say pointing at bacteria — the microbiome.
Mice that stopped smoking expended more energy (i.e. extracted more energy from food) than non-smokers or antibiotic-treated mice (apparently you can work this out by counting fecal calories).
A further key finding was that exposure to smoke caused a major switch in the pattern of expression of genes involved in cell signalling and metabolism, as deduced from analysis of fecal and plasma samples. Notably, a shift in tobacco-exposed gut microbiomes increased the conversion of choline into dimethylglycine (DMG). DMG is an amino acid made from glycine and it may increase energy harvest by the gut. The increased use of glycine lowered levels of N-acetylglycine — a metabolite reduces weight in mice when administered as a supplement.
Effect on mouse weight of fecal microbiome transplantation.
Black line: weight of normal (germ-free) mice. Red line: weight of normal mice after transfer of feces from ex-smokers, showing substantial (about 10%) weight gain in a month. Redrawn from Fluhr et al. 2021.
To look more closely at the role of the gut microbiome in SCWG Fluhr & Co. used fecal microbiome transplantation — meaning that droppings from mice undergoing exposure to smoke (or previously exposed to smoke) were transferred into germ-free mice (lacking all microorganisms) that had not been exposed to smoke. {For the non-squeamish: in these experiments mouse droppings are suspended in sterile salt solution and given to recipient mice via a feeding needle through the mouth and into the oesophagus}.
The critical finding was that transplantation of feces from mice previously exposed to cigarette smoke into mice never exposed to smoke caused excessive weight gain, regardless of diets and mouse strains.
Much additional work in this paper leads to the conclusion that a key effect in weight gain after stopping smoking is a major switch in the make-up of gut bacteria. The upshot is the shunting of dietary choline into dimethylglycine — driving increased gut energy harvest and weight gain.
Mice and men
It remains to be seen how closely mice mimic humans in their response to tobacco smoke. However, Fluhr & Co. included preliminary observations in humans consistent with the mice results. Thus fecal microbiomes from smokers differed from those of non-smokers and smokers had raised levels of plasma choline, betaine and DMG, similar to the mouse model results.
So, as the guys say, “the microbiome-dependent orchestration of SCWG may be exploitable to improve smoking-cessation success and to correct metabolic perturbations even in non-smoking settings”.
Reference
Fluhr, L., Mor, U., Kolodziejczyk, A.A. et al. Gut microbiota modulates weight gain in mice after discontinued smoke exposure. Nature 600, 713–719 (2021).
Betrayed by Nature: The War on Cancer 