NIH Human Microbiome Project - Core Microbiome Sampling Protocol A (HMP-A)

This first clinical study of the Human Microbiome Project (HMP) addresses whether individuals share a core human microbiome. It involves broad determination of the microbiota found in five anatomical sites: the oral cavity, skin, nasal cavity, gastrointestinal tract and vagina. This study will enroll approximately 300 healthy male and female adults, 18-40 years old, from two geographic regions of the US: Houston, TX and St. Louis, MO. The participation of healthy individuals will create a baseline for discovery of the core microbiota typically found in various areas of the human body. The information from this initial study can then be used to help assess the changes in the complement of microbiota found on or within diseased individuals.

• Study Design:
  • Case-Control
• Study Type:
  • Population-Based Control Set
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 300
• Subject Sample Telemetry Report (SSTR)

Inclusion Criteria:

In order to be eligible for participation in this study, subjects must meet the following criteria:

• Male or female subjects 18 years of age, but not more than 40 years of age at the time of enrollment.
• Must be able to provide signed and dated informed consent.
• Healthy subjects willing and able to provide blood, as well as oral cavity, skin, nasal cavity and stool specimens; female subjects must be willing to provide a vaginal specimen and must either have regular menstrual cycles (between 21 and 35 days) or for subjects on hormonal contraception influencing cycle length, have a history of regular 21 to 35 day menstrual cycles prior to initiating hormonal contraception. At study enrollment, female subjects may be using any contraception method except a combination hormone vaginal ring (see Exclusion Criteria).

Exclusion Criteria:

Any subject who meets any of the following criteria will be excluded from participation in this study:

• Body Mass Index greater than or equal to 35 or less than or equal to 18.
• Vital signs outside of acceptable range at Screening Visit, i.e., blood pressure >160/100, oral temperature >100°F, pulse >100.
• Use of any of the following drugs 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 10⁸ cfu or organisms per day) - includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.
• for female subjects, combination hormone vaginal ring for contraception (due to unknown duration of local hormone effects).
• Receipt of nasally-delivered live, attenuated, cold-adapted influenza vaccine within the previous 28 days.
• Use of topical antibiotics or topical steroids on the face, scalp, or neck or on arms, forearms, or hands within the previous 7 days.
• Use of vaginal/vulvar medications, including antifungals, within the previous 7 days. Subjects may continue to use permitted vaginal contraceptives until 48 hours prior to sampling.
• Acute disease at the time of enrollment (defer sampling 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 on-going medical management or medication) pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality, as determined by medical history or physical examination.
• 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 chronic 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 per day.
• Positive test for HIV, HBV or HCV.
• Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired) including HIV infection.
• Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.
• History of active uncontrolled gastrointestinal disorders or diseases including:
• inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis;
• irritable bowel syndrome (IBS) (moderate-severe);
• persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated);
• chronic constipation.
• Regular urinary incontinence necessitating use of incontinence protection garments.
• Female who is pregnant or lactating.
• Condyloma or human papillomavirus (HPV) diagnosis within the previous 2 years.
• Treatment for or suspicion of ever having had toxic shock syndrome.
• For females, history of candidiasis, urinary tract infection, or active STD (specifically chlamydia, gonorrhea, syphilis, genital herpes, trichomoniasis) within the previous 2 months.
• For females, history of vulvar, vaginal or cervical dysplasia within the previous 5 years.
• History of hysterectomy.
• Vaginal pH greater than 4.5 at screening visit.
• Evidence of vulvar or vaginal irritation at screening or on specimen collection day.
• History of psoriasis or recurrent eczema. Childhood eczema that has resolved is not exclusionary.
• History of recurrent rashes within the past 6 months.
• At the time of the screening visit or on the specimen collection day:
• acne at sites other than on the face, chest, back or shoulders;
• multiple blisters, pustules, boils, abscesses, erosions or ulcers on the scalp, face, neck, arms, forearms or hands;
• a single blister, pustule, boil, abscess, erosion, ulcer, scab, cut, crack or pink/hyperpigmented patch or plaque at or within 4 cm of the sampling sites; sampling may be deferred until the lesion resolves either without treatment or with local treatment only;
• more than one pink/red scaly patch/plaque anywhere on the body (suggestive of psoriasis or eczema);
• uniformly thickened, cracking, "dry" skin on bilateral palms and/or soles;
• scalp dandruff that does not clear up with over-the-counter dandruff shampoos used daily for 2 weeks;
• disseminated rash (at multiple body sites or extending throughout a broad body area).
• Chronic dry mouth, as assessed through questioning of the subject by an experienced clinician.
• Periodontal pockets equal to or greater than 4 mm. (Mild gingivitis is acceptable.)
• More than 10% of sites with bleeding on probing.
• Evidence of untreated cavitated carious lesions or oral abscesses.
• Evidence of precancerous or cancerous oral lesions.
• Evidence of oral candidiasis.
• Evidence of halitosis, as determined by organoleptic assessment by an experienced clinician.
• More than 8 missing teeth. The missing teeth must be due to 3rd molar extractions and/or teeth extracted for orthodontic purposes, teeth extracted as a result of trauma, or teeth that are congenitally missing.

This study is part of the NIH Road Map Human Microbiome Project. The first subject was enrolled on November 24, 2008.

• Primary Phenotype: Metagenomics
• Metagenome

• Principal Investigator
  • James Versalovic, MD, PhD. Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
• Co-Investigators
  • Wendy Keitel, MD. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  • Joseph Petrosino,PhD. Baylor College of Medicine, Houston, TX, USA.
  • Mark Watson, MD, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Michael Dunne, PhD. Washington University School of Medicine, St. Louis, MO, USA.
• Funding Sources
  • U54-HG003273. National Institutes of Health, Bethesda, MD, USA.
  • U54-HG003079. National Institutes of Health, Bethesda, MD, USA.