Condition category
Nutritional, Metabolic, Endocrine
Date applied
02/02/2018
Date assigned
23/02/2018
Last edited
22/02/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
There is increasing interest in studying the relationship between disease and the microbial communities inhabiting the human gut. However, relatively little is known about the impact of dietary patterns and other environmental influences on gut microbial composition, making identification of disease-specific microbial signatures in patient populations with a variable diet problematic. In particular, it has been observed in both mice and humans that the composition of fecal microbiota differs in obese versus lean individuals, prompting the hope that interventions targeting the gut microbiota may offer a viable complementary strategy for combating obesity moving forward. However, it remains to be shown that these differences are not directly attributable to the dietary habits of the individuals in question. Indeed, previous studies in humans have contrasted the effects of certain types of dietary interventions (e.g. plant-based versus animal-based diets) on the gut microbiome, giving us a coarse-grained appreciation of the microbial patterns associated with diet. This study aims to probe the specifics of diet-related microbial signatures by observing the effect of different dietary supplements on the gut microbiota of health individuals. The effect of introducing particular dietary supplements, such as specific types of dietary fibers or omega-3 fats, will be compared between these two populations, and further examine whether diet-related changes can explain the differences between their microbial compositions. In addition, the information can be used to correct for strong correlations between diet and the microbiome in analyses aiming to identify gut microbial signatures involved in a variety of human diseases.

Who can participate?
Adults aged 18-70 who have a BMI between 18-25 or above 30.

What does the study involve?
Participants provide stool samples on two consecutive days as baseline, during which participants consume their ordinary diet, as desired. In the evening of the second day, participants perform a bowel cleanse with PEG, and the following morning begin a period of six days during which their diet is fixed. The diet of the first three days are common to all participants, and consists of water and a nutritional meal replacement (Ensure) ad libitum. This is then followed by a further three days during which participants consume the nutritional meal replacement in addition to a specific micronutrient supplement to which they were randomized at the beginning of the study. Supplements considered include inulin, pectin, cellulose, fish oil, coconut oil and protein powder. Participants are then instructed to resume their normal diet after day 6, and follow up samples are collected one day and one week after resuming their ordinary diet. Stool samples are collected daily (or, failing that, as often as possible), and processed for 16S rRNA and metagenomics sequencing to assess the effect on the composition of the microbiota.

What are the possible benefits and risks of participating?
There are no anticipated benefits or risks to participants of the study.

Where is the study run from?
Massachusetts Institute of Technology (USA)

When is the study starting and how long is it expected to run for?
June 2015 to December 2017

Who is funding the study?
MIT Center for Microbiome Informatics and Therapeutics (USA)

Who is the main contact?
Professor Eric Alm (Public)
Dr Thomas Gurry (Scientific)

Trial website

Contact information

Type

Public

Primary contact

Prof Eric Alm

ORCID ID

http://orcid.org/0000-0001-8294-9364

Contact details

MIT Center for Microbiome Informatics and Therapeutics
500 Technology Square
Cambridge
02139
United States of America

Type

Scientific

Additional contact

Dr Thomas Gurry

ORCID ID

Contact details

MIT Center for Microbiome Informatics and Therapeutics
500 Technology Square
Cambridge
02139
United States of America

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

123456

Study information

Scientific title

Predictability and persistence of prebiotic dietary supplementation in a healthy human cohort

Acronym

Study hypothesis

The study is based on the hypothesis that controlling dietary background will allow for higher resolution in our ability to discern individual bacterial species that respond to prebiotics.

Ethics approval

MIT Committee on the Use of Humans as Experimental Subjects, 29/06/2015, ref#: 1504007066.

Study design

Interventional non randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Other

Patient information sheet

No participant information sheet available

Condition

Diet and the microbiome

Intervention

This study aims to identify the microbial responders to specific micronutrients in the human diet. By placing a cohort of approximately 50 healthy human individuals on a diet consisting entirely of a nutritional meal replacement milkshake and water, and controlling for dietary background, and against this background, supplement the participants' diet with individual micronutrients. Stool samples are collected and the bacterial DNA in them are sequenced to quantify the bacterial communities and the abundances of specific bacteria in each sample. In this manner, we are able to measure the effect of specific prebiotic supplements on the composition of the human gut microbiome.

Participants are placed on a diet consisting entirely of a liquid nutritional meal replacement for three days, and then for three further days in addition to a prebiotic spike-in of choice; microbiome composition is measured throughout the course of the intervention.

The study involves comparing the effects of a controlled diet in contrast to a variable diet on the composition of the gut microbiota. The methodology involves obtaining stool samples on two consecutive days as baseline, during which participants consume their ordinary diet, as desired. In the evening of the second day, participants perform a bowel cleanse with PEG, and the following morning begin a period of six days during which their diet is fixed. The composition of the diet on the first three days are common to all participants, and consists of water and a nutritional meal replacement (Ensure) ad libitum. This is then followed by a further three days during which participants consume the nutritional meal replacement in addition to a specific micronutrient supplement to which they were randomized at the beginning of the study. Supplements considered include inulin, pectin, cellulose, fish oil, coconut oil and protein powder. Participants are then instructed to resume their normal diet after day 6, and follow up samples are collected one day and one week after resuming their ordinary diet. Stool samples are collected daily (or, failing that, as often as possible), and processed for 16S rRNA and metagenomics sequencing to assess the effect on the composition of the microbiota.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

Gut Microbiota composition is measured using the stool samples collected on the two first baseline days and on each day during the provided dietary regimen. This consists of a maximum of 10 stool samples (two baseline, six intervention, and two follow-up), which are sequenced for the 16S rRNA gene.

Secondary outcome measures

The effect of the diet on the microbiota at the level of genes and bacterial strains are processed for metagenomics sequencing at the second baseline sample, day 3 sample, and day 6 sample.

Overall trial start date

29/06/2015

Overall trial end date

31/12/2017

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Individuals between 18-70 years of age
2. BMI between 18-25 or above 30
3. A waist-to-hip ratio of more than 0.9

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

75

Participant exclusion criteria

1. Food allergies
2. Inability to comply with study procedure
3. Suffer from IBS, IBD, Type-2 diabetes, kidney disease or intestinal obstruction
4. Allergic to polyethylene glycol
5. Have received antibiotics in the last 6 months
6. Have untreated, in situ colorectal cancer
7. Are currently pregnant, planning to get pregnant in the next 60 days, or currently breastfeeding

Recruitment start date

01/07/2015

Recruitment end date

01/12/2017

Locations

Countries of recruitment

United States of America

Trial participating centre

Massachusetts Institute of Technology
500 Technology Square
Cambridge
02139
United States of America

Sponsor information

Organisation

MIT Center for Microbiome Informatics and Therapeutics

Sponsor details

500 Technology Square
Cambridge
02139
United States of America

Sponsor type

Research organisation

Website

microbiome.mit.edu

Funders

Funder type

University/education

Funder name

MIT Center for Microbiome Informatics and Therapeutics

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We are currently undergoing peer-review and anticipate publication in a peer reviewed journal in early to mid-2018. No additional documents are available.

IPD sharing statement:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/06/2018

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes