Nicotine’s Unanticipated Impact on Gut Microbiota and Metabolism

Nicotine’s Unanticipated Impact on Gut Microbiota and Metabolism

A recent Scientific Reports study investigates the impact of nicotine exposure on host nutritional status, gut microbial metabolites, and metabolic homeostasis.


The gut microbiome is associated with many physiological functions that include metabolic homeostasis. Several studies have revealed that gut microbiome dysbiosis leads to the development of many metabolic disorders, such as type 2 diabetes mellitus.

Gut microbiota synthesizes a broad spectrum of bioactive metabolites that signal messengers and indicators of microbial function.

The composition and function of these microbes are modulated via diet and daily environmental factors. Host metabolism is significantly affected by diet-derived metabolites synthesized by gut bacteria.

Fermentation of indigestible polysaccharides by gut microbe leads to the generation of short-chain fatty acids (SCFA), which improves weight gain resistance and insulin sensitivity.

The gut microbiota is associated with synthesizing diverse fatty acid variants, such as hydroxy-, conjugated-, and oxy-fatty acids, which promotes host resistance to high-fat diet (HFD)-induced obesity.

The synthesis of fatty acid metabolites by gut microbiota, depending on the dietary environment of the host, plays a crucial role in improving host metabolic functions.

Cigarette smoking is a key preventable factor that enhances mortality. The majority of smokers are susceptible to developing cardiovascular issues, chronic obstructive pulmonary disease (COPD), and various types of cancers.

Several studies have also indicated that exposure to second-hand smoke contributes to the development of pathogen-related infections and aggravates asthma, inflammatory bowel disease, and Crohn’s disease.

Nicotine is the primary active ingredient in tobacco. Besides being absorbed by the pulmonary alveoli, they are also found in the skin and gastrointestinal tract. Many beneficial and detrimental effects of nicotine have been identified.

ALSO READ  E-Cigarettes Outperform Traditional Nicotine-Replacement Therapies in Smoking Cessation Success

As per the benefits, nicotine regulates energy intake by modulating appetite. As regards the detrimental effects, previous studies have documented evidence that indicated how nicotine exposure leads to the development of hepatic steatosis and cardiovascular diseases. 

Nicotine exposure can alter host metabolism by inducing changes in the gut microbiota and its metabolites.

It is imperative to understand the underlying mechanism that controls the interplay between gut environment, diet-derived microbial metabolites, and host metabolic homeostasis against nicotine exposure.

About the study

The current study evaluated how nicotine exposure affected the metabolic regulatory mechanisms by inducing changes in gut microbial composition and their metabolic products.

A mouse model was used to understand the underlying mechanism responsible for the observed effect. A global meta-analysis was conducted to understand how nicotine exposure alters gut microbiota, affecting host metabolism.

For experimental purposes, seven-week-old male mice with comparable body weights were divided into two groups: the normal diet (ND) group and the high-fat diet (HFD) group.

These mice were exposed to nicotine or saline for four weeks. After seven to eleven weeks of intervention, SCFAs and long-chain fatty acid metabolite levels were estimated.

The body weight of the study mice was also measured once a week. Blood samples were collected for analysis.

Study findings

The current study reflects the intense interplay of the gut microbiota and their metabolites and host metabolic characteristics in the backdrop of nicotine exposure.

Intraperitoneal nicotine administration was found to have a profound effect on weight regulation and metabolic phenotypes. This effect was independent of reduced caloric intake.

ALSO READ  Zyn Nicotine Pouches Viral on TikTok: Stirring Debate Among Politicians and Health Experts

Mechanistically, the nicotine-induced body weight suppression was modulated by specific gut bacteria, including Lactobacillus spp, synthesizing KetoB (linoleic acid) during HFD intake alone.

Several studies have shown that nicotine decreases body weight and food intake via the hypothalamic melanocortin system.

A decrease in the relative abundance of Lactobacillus spp. occurred in response to high HFD exposure. This bacterial population spiked in the presence of nicotine, particularly under HFD conditions.

The pair-feeding model in this study indicated that the main mechanism of weight control induced by nicotine administration was linked to decreased caloric intake. No specific correlation was observed between caloric intake and body weight even under ad libitum conditions. 

Although nicotine administration resulted in a reduction in caloric intake in both ND and HFD groups, a greater reduction in body weight specifically occurred in the HFD group.

This result indicates that diet-dependent factors contribute to weight loss triggered by nicotine treatment. An elevated concentration of LCFAs that impacted gut microbial sensitivity to nicotine was found in the HFD group.

The increase in plasma non-esterified fatty acid (NEFA) after intraperitoneal nicotine administration in HFD-fed mice indicates the role of nicotine in promoting lipolysis.

The gut microbiota depletion model using antibiotic treatment in HFD-fed mice revealed that gut microbiota and their dietary fatty acid-derived metabolites are crucial in nicotine-induced body weight loss. The treated mice also significantly reduced caloric intake following nicotine administration.


The current study identified Keto B as a regulator of body weight loss associated with nicotine administration.

It highlighted the broad interplay of gut microbe in response to smoking that influences varied metabolic conditions including lowering of body weight.

ALSO READ  E-Cigarettes Outperform Traditional Nicotine-Replacement Therapies in Smoking Cessation Success

Notably, the use of microbes in weight reduction has been reflected in this study.


Most read