Microbial, Immune, and Metabolic Perturbations by Antibiotics (MIME Study)

• SUBJECT INCLUSION CRITERIA:

Healthy women and men will be eligible for study participation if they meet the following criteria:

• A participant will have passed his/her 18th birthday and will not have attained the age of 50 at the time of enrollment.
• Willing to allow storage of their biological samples.
• Able to comply with study procedures and swallow capsules.

SUBJECT EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from study participation:

• Body Mass Index (BMI) greater than or equal to 35 or less than or equal to 18 kg/M(2).
• Vital signs outside of acceptable range at Screening Visit, i.e., blood pressure >160/100, oral temperature >100 degrees F, pulse >100.

• Use of any of the following drugs or devices within the last 6 months:

  • systemic antibiotics, antifungals, antivirals, or antiparasitics (intravenous, intramuscular, or oral);
  • oral, intravenous, intramuscular, nasal, or inhaled corticosteroids;
  • cytokines;
  • methotrexate or immunosuppressive cytotoxic agents;
  • large doses of commercial probiotics consumed (greater than or equal to 10(8) cfu or organisms per day), including tablets, capsules, lozenges, chewing gum, or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, and foods do not apply.
  • anabolic steroids;
  • intrauterine device, combination hormone vaginal ring for contraception (due to unknown duration of local hormone effects), topical or systemic estrogens. Oral contraceptives with a standard 28-day cycle will be permitted if the subject has been consistently taking them for at least 1 month;
  • oral, topical, intramuscular testosterone preparations.
• Illicit drug use, including amphetamines, cocaine, or heroin, within the last 6 months. Marijuana use is not exclusionary.
• Chronic smokers and subjects who use smokeless tobacco products (due to known effects of tobacco on the oral microbiome).
• Claustrophobia.
• Use of antacids (proton pump inhibitors, sucralfate, H1 and H2 antagonists, and those containing aluminum magnesium) within the last 3 months.
• Use of laxatives or enemas within the last 3 months.
• Diagnostic colonoscopy within the last 6 months.
• Use of topical antibiotics or topical steroids on the face, scalp, or neck, or on arms, forearms, or hands within the previous 30 days.
• Use of vaginal/vulvar medications, including antifungals, within the previous 30 days. Subjects may continue to use permitted vaginal contraceptives (spermicides and female condoms) until 24 hours prior to sampling
• Use of isotretinoin within the past 5 years.
• Intranasal influenza vaccination within the last 6 months due to effects on mucosal immunity.
• Acute disease at the time of enrollment (defer enrollment until subject recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever.

• Chronic, clinically significant (unresolved, requiring ongoing medical management or medication) pulmonary, cardiovascular, dermatologic, endocrine, GI, hepatic, or renal functional abnormality, as determined by medical history, physical examination, and/or laboratory testing. Includes, but not limited to:

  • A history of diabetes mellitus (Type 1 or 2), pituitary disease, hypothyroidism, hyperthyroidism
  • A history of physician-diagnosed asthma
  • A history of allergy to any antibiotic medications, including amoxicillin (penicillin) and/or azithromycin (macrolide)
  • A history of food allergy requiring dietary accommodation
  • Lactose-intolerance requiring dietary accommodation
  • A history of a bleeding disorder
  • Mononucleosis
  • Liver disease, including non-alcoholic fatty liver disease, AST or ALT > 1.5 times normal value, cirrhosis
  • Renal disease, as defined by serum creatinine concentrations > 1.5 mg/dL and/or overt proteinuria
  • Central nervous system disease, including previous history of cerebrovascular accidents, dementia, and neurodegenerative disorders
  • Clinically significant abnormal results on electrocardiogram (ECG) that in the opinion of the PI, would place the patient at increased risk of QT-prolongation or other cardiac event

• Genitourinary/Gynecologic conditions, including:

  • Treatment for or suspicion of ever having had toxic shock syndrome
  • History of hysterectomy or oophorectomy
  • History of condyloma or human papillomavirus diagnosed within the previous 2 years
  • History of candidiasis, urinary tract infection, or sexually transmitted disease (specifically chlamydia, gonorrhea, syphilis, genital herpes, trichomoniasis) diagnosed within the previous 6 months
  • Evidence (by history or physical exam) of vulvar or vaginal irritation at screening
  • History of vulvar, vaginal, or cervical dysplasia within the previous 5 years
• History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
• Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
• Recent history of excessive alcohol consumption defined as more than five 1.5-ounce servings of 80-proof distilled spirits, five 12-ounce servings of beer, or five 5-ounce servings of wine at one sitting over the last 30 days.
• Positive test for HIV, hepatitis B virus, or hepatitis C virus indicating infection (hepatitis B seropositivity conferred by vaccination is not exclusionary).
• Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired).
• Major surgery of the GI tract, including cholecystectomy or appendectomy, in the past 5 years. Any major bowel resection at any time.
• History of gastric stapling, lap band, or surgical procedure for treatment of obesity.

• History of GI disorders or diseases including:

  • inflammatory bowel disease (IBD) including ulcerative colitis, Crohn s disease (of any severity), or indeterminate colitis;
  • irritable bowel syndrome (IBS);
  • persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent), gastric or duodenal ulcer;
  • Celiac disease;
  • chronic constipation.
• Active behavioral or psychiatric conditions that would be incompatible with a safe and successful participation in the study, including major depression, anxiety disorder, schizophrenia, and presence of psychotic symptoms.
• Active eating disorders, including anorexia nervosa, bulimia, or binge eating syndrome.
• Use of weight-loss drugs within the past 5 years.
• Weight change (intended or unintended; loss or gain) of more than 10% of total body weight in the 3 months before admission.
• Regular urinary incontinence necessitating use of incontinence protection garments.
• Female who is pregnant, intending to become pregnant, or lactating.
• History of recurrent rashes within the past 6 months.

• At the time of the screening visit:

  • multiple blisters, pustules, boils, abscesses, erosions or ulcers on the scalp, face, neck, arms, forearms, or hands;
  • uniformly thickened, cracking, dry skin on bilateral palms and/or soles;
  • disseminated rash (at multiple body sites or extending throughout a broad body area).
• Subjects who are unable to complete required study visits per allotted visit windows.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.