Nicotine’s Appetite-Suppressing Effects Are Driven by the Gut Microbiota

An estimated 1.3 billion people use tobacco products globally. Although the dangers of smoking are well established, the effects of nicotine – the primary ingredient of tobacco – on health and metabolism are only recently being unveiled.

In a new study, published in Scientific Reports, researchers from Kyoto University explored the role of nicotine on weight management through host metabolism and gut microbial metabolites.

Nicotine and host health

The composition of the gut microbiome is affected by a myriad of external and internal factors, from diet to stress and even geographical location. The microbiome has also been associated with weight management – several studies have demonstrated weight fluctuations can significantly alter the microbiome.

The inhalation of cigarette smoke is a lifestyle factor that has been linked to gut microbiome dysbiosis, with researchers reporting an increase in the abundance of Bacteroidetes in the gut microbiota of smokers compared to non-smokers. While previous claims have led some people to believe nicotine itself is relatively harmless, recent studies have found this may not always be the case. Nicotine can provide some benefits to the body, though, including potentiation of metabolic rate and regulation of energy intake by modulating appetite. Several epidemiological studies have also demonstrated a robust association between cigarette smoking, smoking cessation and body weight fluctuation.

“Interestingly, it has been reported that weight gain following smoking cessation may be associated with a transition to a gut microbiota profile similar to the recently identified ‘obese microbiota’ observed in both human and animal studies,” the authors of the new study wrote.

In the new study, the researchers wanted to understand how nicotine administration might affect microbial metabolites, and therefore influence metabolism and weight.

Nicotine-sensitive metabolites

The researchers from used mice models split into two groups, a normal diet (ND) group and a high-fat diet (HFD) group to investigate whether the effects of nicotine were diet-dependent. The mice were administered nicotine or a saline solution twice a day for four weeks and bodyweights were recorded weekly. After 7-11 weeks, fecal samples were collected to anayze their microbiome composition and the levels of both short-chain fatty acids and long-chain fatty acid (LCFA). Blood samples were also collected.

Nicotine administration resulted in a reduction in body weight in both groups that was not attributed to a reduction in calorie consumption. “There was no precise correlation between caloric intake and body weight even under ad libitum conditions,” the authors wrote. 

A greater reduction in body weight was observed in the HFD group, suggesting that diet-dependent factors contributed to the weight loss induced by nicotine treatment.

The authors found an association between nicotine-induced bodyweight suppression and changes in the gut microbiota composition in the HFD group; specifically, an increase in the abundance of Lactobacillus. They also observed an increase in nicotine-sensitive LCFAs in the HFD group compared to the ND group, notably KetoB – a LCFA produced by Lactobacillus. The results suggest that KetoB may play a role in the weight-reducing effects of nicotine administration under HFD feeding conditions.

Understanding nicotine’s role in modulating host metabolism

The research team highlighted the role in nicotine in weight management was shown to be diet-dependant. The observed effects were found to be linked to changes in the gut microbiota, particularly the genus Lactobacillus, and specific nicotine-sensitive microbial metabolites, notably KetoB.

The study outlines the complex interplay between nutritional control and the gut environment on host metabolism driven by nicotine treatment, however, further studies are required to understand the precise regulatory mechanisms of the gut microbiome and its metabolites, in response to nicotine exposure.

The authors concluded, “Identifying the host receptor for KetoB produced by functional alterations in the gut microbiome in response to nicotine exposure and the subsequent regulation of metabolic homeostasis requires detailed follow-up investigations,” the authors concluded,

Reference: Ohue-Kitano R, Banno Y, Masujima Y, Kimura I. Gut microbial metabolites reveal diet-dependent metabolic changes induced by nicotine administration. Sci Rep. 2024;14(1):1056. doi: 10.1038/s41598-024-51528-3