Effects of Smoking and Smoking Cessation on the Intestinal Microbiota

Introduction: We evaluated associations of smoking heaviness markers and the effects of smoking cessation on the intestinal microbiota and cardiovascular disease risk factors in current smokers undertaking a quit attempt. Methods and Results: Participants were current smokers enrolled in a randomized clinical trial of smoking cessation therapies with visits, risk factor measurements, and fecal collections at baseline, 2, and 12 weeks after starting a quit attempt. Genomic DNA was extracted from fecal samples followed by 16S rRNA gene sequencing and analysis using the QIIME2 software workflow. Relative abundances of bacterial taxa and alpha- and beta- diversity measures were compared. Longitudinal changes in bacterial taxa abundances were compared using analysis of covariance (ANCOVA). The 36 smokers were (mean [standard deviation]) 51.5 (11.1) years old (42% male) and smoked 15.1 (6.4) cigarettes per day for 22.7 (11.9) pack-years. Their exhaled carbon monoxide (CO) levels were 17.6 (9.3) ppm. At baseline, relative abundances of the phylum Actinobacteria were correlated inversely with pack-years (rho=-0.44, p=0.008) and Cyanobacteria were correlated positively with CO levels (rho=0.39, p=0.021). After 12 weeks, abundances of the phylaBacteroidetes increased (pANCOVA=0.048) and Firmicutes decreased (pANCOVA=0.036) among abstainers compared to continuing smokers. Increases in alpha-diversity were associated with lower heart rates (rho=-0.59, p=0.037), systolic blood pressures (rho=-0.58, p=0.043), and C-reactive protein levels (rho=-0.60, p=0.034). Conclusions: Smoking cessation leads to minor changes in the intestinal microbiota. It is unclear if the proven health benefits of smoking cessation lead to salutary changes in the intestinal microbiota and if such changes affect cardiovascular disease risk.

[1]  Francesco Asnicar,et al.  Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2 , 2019, Nature Biotechnology.

[2]  A. Palloni,et al.  Close social relationships correlate with human gut microbiota composition , 2019, Scientific Reports.

[3]  Su Hwan Lee,et al.  Association between Cigarette Smoking Status and Composition of Gut Microbiota: Population-Based Cross-Sectional Study , 2018, Journal of clinical medicine.

[4]  S. Hazen,et al.  Development of a gut microbe-targeted non-lethal therapeutic to inhibit thrombosis potential , 2018, Nature Medicine.

[5]  Z. Savin,et al.  Smoking and the intestinal microbiome , 2018, Archives of Microbiology.

[6]  L. Kasselman,et al.  The gut microbiome and elevated cardiovascular risk in obesity and autoimmunity. , 2018, Atherosclerosis.

[7]  M. Fischbach,et al.  The Biosynthesis of Lipooligosaccharide from Bacteroides thetaiotaomicron , 2018, mBio.

[8]  F. Bushman,et al.  Publisher Correction: Enterotypes in the landscape of gut microbial community composition , 2018, Nature Microbiology.

[9]  Benjamin D. Kaehler,et al.  Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2’s q2-feature-classifier plugin , 2018, Microbiome.

[10]  T. Weir,et al.  The gut microbiota as a novel regulator of cardiovascular function and disease. , 2017, The Journal of nutritional biochemistry.

[11]  B. Yandell,et al.  Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes. , 2017, Cell reports.

[12]  Megan E. Piper,et al.  Longitudinal Impact of Smoking and Smoking Cessation on Inflammatory Markers of Cardiovascular Disease Risk , 2017, Arteriosclerosis, thrombosis, and vascular biology.

[13]  Paul J. McMurdie,et al.  DADA2: High resolution sample inference from Illumina amplicon data , 2016, Nature Methods.

[14]  J. Nicholson,et al.  Impact of the gut microbiota on inflammation, obesity, and metabolic disease , 2016, Genome Medicine.

[15]  Nathan Crook,et al.  The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation , 2016, Genome Medicine.

[16]  S. Hazen,et al.  Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis , 2015, Cell.

[17]  F. Turroni,et al.  Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus , 2014, mBio.

[18]  S. Hazen,et al.  Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry. , 2014, Analytical biochemistry.

[19]  S. Hazen,et al.  Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. , 2013, The New England journal of medicine.

[20]  Ateequr Rehman,et al.  Smoking Cessation Induces Profound Changes in the Composition of the Intestinal Microbiota in Humans , 2013, PloS one.

[21]  F. Bushman,et al.  Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis , 2013, Nature Medicine.

[22]  S. Ng,et al.  Smokers with active Crohn's disease have a clinically relevant dysbiosis of the gastrointestinal microbiota* , 2012, Inflammatory bowel diseases.

[23]  Eric P. Nawrocki,et al.  An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea , 2011, The ISME Journal.

[24]  B. Finlay,et al.  Shifting the balance: antibiotic effects on host–microbiota mutualism , 2011, Nature Reviews Microbiology.

[25]  Brian J. Bennett,et al.  Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease , 2011, Nature.

[26]  Jennifer C. Drew,et al.  Toward defining the autoimmune microbiome for type 1 diabetes , 2011, The ISME Journal.

[27]  Megan E. Piper,et al.  Effects of smoking and smoking cessation on endothelial function: 1-year outcomes from a randomized clinical trial. , 2010, Journal of the American College of Cardiology.

[28]  Ruth E Ley,et al.  Obesity and the human microbiome , 2010, Current opinion in gastroenterology.

[29]  A. Schwiertz,et al.  Microbiota and SCFA in Lean and Overweight Healthy Subjects , 2010, Obesity.

[30]  T. Vogel,et al.  Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes , 2009, Environmental health perspectives.

[31]  R. Knight,et al.  The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice , 2009, Science Translational Medicine.

[32]  R. Parker,et al.  Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s. , 2008, Journal of the American College of Cardiology.

[33]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

[34]  David Gonzales,et al.  Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation: A Randomized Controlled Trial , 2006 .

[35]  R. Knight,et al.  UniFrac: a New Phylogenetic Method for Comparing Microbial Communities , 2005, Applied and Environmental Microbiology.

[36]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[37]  E. C. Pielou.  The measurement of diversity in different types of biological collections , 1966 .