10/8/2015. Cigarette Smoking is Associated with an Altered Metabolomic Profile in the Vaginal Tract. The Vaginal Microbiome & Bacterial Vaginosis:

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Sheena French
5 years ago
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Joanna-Lynn Borgogna 1, Rebecca Brotman 2 & Carl Yeoman 1 1 M o n t a n a S t a t e U

age 15 smoke tobacco Tobacco Atlas, 2013 Global Percentage of Female Smokers: Tobacco

MOUTH LUNG CANCER ASTHMA CHRONIC OBSTRUCTIVE PULMONARY DISEASE CERVICAL CANCER EARLY

DISEASE GASTRIC CANCER COLON CANCER 250 million women world wide smoke daily Tobacco

Microbiome & Bacterial Vaginosis: Most common vaginal disorder amongst reproductive

5 Discharge Clue cells Associated with: Pre-term birth (PTB) Miscarriage Pelvic

1 Cigarette Smoking is Associated with an Altered Metabolomic Profile in the Vaginal Tract Annual Global Number of Cigarettes Smoked Per Person: Tiffanie Nelson 1, Joanna-Lynn Borgogna 1, Rebecca Brotman 2 & Carl Yeoman 1 1 M o n t a n a S t a t e U n i v e r s i t y 2 U n i v e r s i t y o f M a r y l a n d 21% of global population age 15 smoke tobacco Tobacco Atlas, 2013 Global Percentage of Female Smokers: Tobacco Use Negatively Impacts Health: BLINDNESS IMPAIRED SENSE OF SMELL CANCER OF LIPS AND MOUTH LUNG CANCER ASTHMA CHRONIC OBSTRUCTIVE PULMONARY DISEASE CERVICAL CANCER EARLY MENOPAUSE REDUCED FERTILITY ESOPHOGEAL CANCER TRACHEAL CANCER LARYNX CANCER HEART DISEASE GASTRIC CANCER COLON CANCER 250 million women world wide smoke daily Tobacco Atlas, 2013 WHO, 2014 The Vaginal Microbiome & Bacterial Vaginosis (BV) The Vaginal Microbiome & Bacterial Vaginosis: Most common vaginal disorder amongst reproductive aged women Amsel Criteria Fishy odor Vaginal ph >4.5 Discharge Clue cells Associated with: Pre-term birth (PTB) Miscarriage Pelvic inflammatory diseases Vaginal Microbiome Community of native bacteria that colonize the vaginal tract First line of defense against contracting vaginal diseases 1

The Vaginal Microbiome: Community State Types (CST) The low Lactobacillus Community State - V: Low Lactobacillus V Lactobacillus jensenii CST V 5%

PNAS 2011 II 35% I 6% Lactobacillus gasseri Lactobacillus iners High ph 5.

2014 II 35% I 6% Smoking and the Vaginal Microbiome: Part 1 How does smoking impact the vaginal microbiome?

Smoking and the Vaginal Microbiome: Pilot Study: 20 non-smokers 20 smokers Self-collected vaginal swabs Microbiome analysis using 454 16S rrna gene

2 The Vaginal Microbiome: Community State Types (CST) The low Lactobacillus Community State - V: Low Lactobacillus V Lactobacillus jensenii CST V 5% Lactobacillus crispatus V is characterized by: Higher diversity of ananerobic Species Prevotella Dialister Streptococcus V CST V 5% Ravel et al. PNAS 2011 II 35% I 6% Lactobacillus gasseri Lactobacillus iners High ph 5.3 Associated with increased risk for common urogenital disorders & STIs Ravel et al. PNAS 2011; Brotman et al BMC Infect. Dis II 35% I 6% Smoking and the Vaginal Microbiome: Part 1 How does smoking impact the vaginal microbiome? Part 2 How does smoking affect the vaginal metabolome? Smoking and the Vaginal Microbiome: Pilot Study: 20 non-smokers 20 smokers Self-collected vaginal swabs Microbiome analysis using S rrna gene sequencing Brotman et al BMC Infect. Dis Smoking Negatively Affects the Microbiome: 50% of smokers versus 15% of non-smokers were classified to vaginal CST-IV (low-lactobacillus ) Smoking and Reproductive Health: How does smoking impact the vaginal tract and women s reproductive health? Part 1 How does smoking impact the vaginal microbiome? Part 2 How does smoking affect the vaginal metabolome? Brotman et al BMC Infect. Dis

Metabolome: Metabolome is Closely Tied to Phenotype:

biological sample ENDOGENOUS EXOGENOUS Sampling Method

and s 619 metabolites were detected nicotine cotinine

3'-monophosphate (3'-AMP) nicotinate pyroglutamylvaline

01 100 Tobacco Constituents are Much Higher in Smokers

3 Metabolome: Metabolome is Closely Tied to Phenotype: Complete set of small-molecule chemicals found within a biological sample ENDOGENOUS EXOGENOUS Sampling Method for Metabolomics: Metabolite Differences between Smokers and s 619 metabolites were detected nicotine cotinine hydroxycotinine 3-hydroxycotinine glucuronide tryptamine deoxycarnitine alpha-hydroxyisovalerate 3-methyl-2-oxovalerate xanthine uracil adenosine 3'-monophosphate (3'-AMP) nicotinate pyroglutamylvaline Tobacco exposure and its metabolites Tobacco Constituents are Much Higher in Smokers Accumulation of TCA Related Compounds in V Smokers: ~75% ~1.5 % Tricarballylate Succinate II V Malate

Accumulation of Vitamin B Compounds in V Smokers Biogenic Amines are Increased in V Smokers Pyridoxate (Vitamin B6) Riboflavin (Vitamin B2) Pantothenate (Vitamin B5) L-Lysine L-Arginine L-Ornithine

2015 Biogenic Amines are Increased in V Smokers Biogenic Amines are Increased in CST Smokers: 0 20 40 60 Relative Concentration Biogenic amines 100 1000 Amino acids Ornithine Lysine II V Conclusions:

4 Accumulation of Vitamin B Compounds in V Smokers Biogenic Amines are Increased in V Smokers Pyridoxate (Vitamin B6) Riboflavin (Vitamin B2) Pantothenate (Vitamin B5) L-Lysine L-Arginine L-Ornithine Tryptophan Agmatine Tryptamine Amino acid Biogenic amine Transformation pathway 0.01 Tyrosine Tyramine Nelson et al Frontiers Pathology. Dis Biogenic Amines are Increased in V Smokers Biogenic Amines are Increased in CST Smokers: Relative Concentration Biogenic amines Amino acids Ornithine Lysine II V Conclusions: Smoking associated with a disrupted microbiota Increases odds of being categorized as V Smoking directly affects the vaginal metabolome and breakdown compounds present in vagina Vitamin B is increased in smokers vs non-smokers suggesting uptake deficiencies Acknowledgements Study Lead: Dr. Rebecca Brotman Institute for Genome Sciences University of Maryland School of Medical Sciences rbrotman@som.umaryland.edu Collaborators Dr. Carl Yeoman, Montana State University Dr. Tiffanie Nelson, Montana State University Dr. Jacques Ravel, University of Maryland Dr. P Gajer, University of Maryland Biogenic amines are increased in smokers vs nonsmokers 4

5 Tobacco Constituents are Much Higher in Smokers Questions? ~75% ~1.5 % II V Accumulation of TCA Related Compounds in V Smokers: Accumulation of Vitamin B Compounds in V Smokers Tricarballylate Pyridoxate (Vitamin B6) Succinate Riboflavin (Vitamin B2) Malate Pantothenate (Vitamin B5) Biogenic Amines are Increased in V Smokers Biogenic Amines are Increased in V Smokers L-Lysine L-Arginine L-Ornithine Tryptophan Agmatine Tryptamine Amino acid Biogenic amine Transformation pathway Ornithine Tyrosine Tyramine Lysine Nelson et al Frontiers Pathology. Dis

6 Biogenic Amines are Increased in CST Smokers: Shifts in Amino Acid Metabolism Implications for Health: Relative Concentration Biogenic amines Kynurenate Amino acids Spermine Spermidine Agmatine Tyramine II V LOG Relative Concentration of Vaginal Metabolites +/- SE 6

Diversity & Dynamics of the Human Vaginal Microbiota. Johanna B. Holm, PhD University of Maryland Baltimore Institute for Genome Sciences

Diversity & Dynamics of the Human Vaginal Microbiota Johanna B. Holm, PhD University of Maryland Baltimore Institute for Genome Sciences Host - Microbe Interactions, The Metaorganism Bosch & McFall-Ngai,