What are we asking people to do?
Very long answer: We’re recruiting healthy, nonpregnant adults between the ages of 18-70 for a 6-9 month study that involves doing 3 things: providing regular stool and urine samples, deliberately perturbing the gut microbiota, and filling out detailed questionnaires. These three elements are explained below, and the ‘Check your eligibility’ button at the bottom of the 'About Our Study' page of the website has more details on who can participate. More than 100 participants are needed for a 35 week sampling protocol with two perturbations, and a small number are needed for a 25 week protocol with a single perturbation.
Sampling: Stool samples are a non-invasive way for us to examine the gut microbiota, and the small molecules present in the urine let us investigate the combined metabolism of the human host and the gut microbiota. (We aren’t studying the microbiota of the urinary system itself.) Participants will collect these samples themselves at home, which takes about 10 minutes, using materials that we provide. Participants will keep the samples in their home freezer until we arrange for transfer of the frozen samples to the lab, which happens several times during the study. If you're in the Stanford area this transfer may happen in person; if you're somewhere else in the U.S., we'll overnight ship a cooler of dry ice to you, and you'll overnight it back to us with your samples. (We pay for the shipping.) During most of the study participants will collect samples once per week, but sampling will be daily in the weeks before, during and after deliberate perturbations of the microbiota, and every 2-3 days in the second week after an antibiotic perturbation. For comparison to these daily sampling intervals, we will also request 5 daily samples during two or three other weeks of the study, at least a month away from deliberate perturbations.
Perturbation: In the study as a whole we are comparing three different perturbations, but individual participants will only experience two of them (or one, for those in the 25-week protocol).
The first perturbation for all participants in the 35-week protocol is diet supplementation with about 4 tablespoons of resistant starch per day for 5 days during week 11. Participants may chose between potato-based and corn-based starch; both are almost-flavorless white powders that can be added to food or drink (but not cooked). Resistant starch is not digested in the stomach or small intestine, but reaches the large intestine where it stimulates the growth of particular strains of bacteria (in most people). It is generally well tolerated, with some people reporting increased flatulence.
The second perturbation in the 35-week protocol (during week 22) is either a course of ciprofloxacin (an antibiotic), or a 1-day colonic cleansing which involves following a clear liquid diet and drinking a solution of a nonabsorbable polymer to induce diarrhea. Participants can chose which of these perturbations they want to experience (until one of the options has all the people necessary). [Update as of spring 2015: we have enough people signed up for the colon cleanout, but we are still recruiting people for the antibiotic perturbation.] The antibiotic course (500 mg of ciprofloxacin, twice daily for 5 days) is typical of what might be prescribed for an uncomplicated urinary tract infection; common side effects include nausea (5.2% of patients), diarrhea (2.3%), and vomiting (2%). The colon cleansing (drinking 12-16 glasses of Go-Lytely® solution in 3-4 hours) is a typical procedure prior to a colonoscopy; participants need to plan on 6-10 hours without other responsibilities because the procedure induces a large volume of diarrhea to empty the colon of partially digested food and fecal material.
Participants in the 25-week protocol will experience ciprofloxacin as the deliberate perturbation during week 13; diet supplementation is not a perturbation option for the shorter sampling protocol.
Questionnaires: We already know that the gut microbiota varies a lot between different people; want to collect detailed information about the participants in our study so that we can better understand the sources of this variability. We will ask participants to fill out a web-based food frequency questionnaire that assesses long-term diet preferences. We will also ask participants to fill out a questionnaire that covers current and past health, family background, where you’ve lived, and aspects of your lifestyle that affect your exposure to environmental and host-associated microbes.
Additional options: We will be asking a subset of participants to participate in additional, optional procedures. Participants can still be part of the study involving the procedures described above, if they decide not to participate in the optional procedures. The optional procedures are: providing blood samples (2-3 tablespoons) either once or multiple times before, during and after perturbations, participating in genetic testing and gene expression profiling for human genes, participating in physiological testing before and after ciprofloxacin perturbation, and providing additional follow-up samples (e.g. monthly) after the main sampling intervals described above.
Sampling: Stool samples are a non-invasive way for us to examine the gut microbiota, and the small molecules present in the urine let us investigate the combined metabolism of the human host and the gut microbiota. (We aren’t studying the microbiota of the urinary system itself.) Participants will collect these samples themselves at home, which takes about 10 minutes, using materials that we provide. Participants will keep the samples in their home freezer until we arrange for transfer of the frozen samples to the lab, which happens several times during the study. If you're in the Stanford area this transfer may happen in person; if you're somewhere else in the U.S., we'll overnight ship a cooler of dry ice to you, and you'll overnight it back to us with your samples. (We pay for the shipping.) During most of the study participants will collect samples once per week, but sampling will be daily in the weeks before, during and after deliberate perturbations of the microbiota, and every 2-3 days in the second week after an antibiotic perturbation. For comparison to these daily sampling intervals, we will also request 5 daily samples during two or three other weeks of the study, at least a month away from deliberate perturbations.
Perturbation: In the study as a whole we are comparing three different perturbations, but individual participants will only experience two of them (or one, for those in the 25-week protocol).
The first perturbation for all participants in the 35-week protocol is diet supplementation with about 4 tablespoons of resistant starch per day for 5 days during week 11. Participants may chose between potato-based and corn-based starch; both are almost-flavorless white powders that can be added to food or drink (but not cooked). Resistant starch is not digested in the stomach or small intestine, but reaches the large intestine where it stimulates the growth of particular strains of bacteria (in most people). It is generally well tolerated, with some people reporting increased flatulence.
The second perturbation in the 35-week protocol (during week 22) is either a course of ciprofloxacin (an antibiotic), or a 1-day colonic cleansing which involves following a clear liquid diet and drinking a solution of a nonabsorbable polymer to induce diarrhea. Participants can chose which of these perturbations they want to experience (until one of the options has all the people necessary). [Update as of spring 2015: we have enough people signed up for the colon cleanout, but we are still recruiting people for the antibiotic perturbation.] The antibiotic course (500 mg of ciprofloxacin, twice daily for 5 days) is typical of what might be prescribed for an uncomplicated urinary tract infection; common side effects include nausea (5.2% of patients), diarrhea (2.3%), and vomiting (2%). The colon cleansing (drinking 12-16 glasses of Go-Lytely® solution in 3-4 hours) is a typical procedure prior to a colonoscopy; participants need to plan on 6-10 hours without other responsibilities because the procedure induces a large volume of diarrhea to empty the colon of partially digested food and fecal material.
Participants in the 25-week protocol will experience ciprofloxacin as the deliberate perturbation during week 13; diet supplementation is not a perturbation option for the shorter sampling protocol.
Questionnaires: We already know that the gut microbiota varies a lot between different people; want to collect detailed information about the participants in our study so that we can better understand the sources of this variability. We will ask participants to fill out a web-based food frequency questionnaire that assesses long-term diet preferences. We will also ask participants to fill out a questionnaire that covers current and past health, family background, where you’ve lived, and aspects of your lifestyle that affect your exposure to environmental and host-associated microbes.
Additional options: We will be asking a subset of participants to participate in additional, optional procedures. Participants can still be part of the study involving the procedures described above, if they decide not to participate in the optional procedures. The optional procedures are: providing blood samples (2-3 tablespoons) either once or multiple times before, during and after perturbations, participating in genetic testing and gene expression profiling for human genes, participating in physiological testing before and after ciprofloxacin perturbation, and providing additional follow-up samples (e.g. monthly) after the main sampling intervals described above.