Nutritional and Metabolic Diseases
Conditions
Keywords
systemic malodor, body odor, bad breath, PATM, microbiome, TMAU, Malabsorption, Dysbiosis
Brief summary
The purpose of this study is to identify microbial signatures associated with remission and recurrence of idiopathic malodor and PATM conditions.
Detailed description
Human odorprints, mostly owing to the microbiome, have proven their value as biomarkers of health and environmental exposures. In recent years, microbial networks responsible for localized malodors such as halitosis or axillary odor have been mapped by using next generation sequencing approaches. Intestinal microbes responsible for psychologically debilitating systemic malodor (whole-body and extraoral halitosis), however, remain to be identified. Even a relatively straightforward disorder of choline metabolism trimethylaminuria (TMAU) is thought to exhibit complex host-gene microbiome interactions and has not been sufficiently studied. Proposed controlled pilot study aims to explore the dynamics of microbial communities in remission and flare-up periods. Better knowledge of the important aspects of disease fluctuation should enhance patient care and, combined with our prior data, will help to develop new therapies and treatments.
Interventions
BEHAVIORALNutritional counselling
Behavioral nutritional counselling delivered via the Internet.
BEHAVIORALStress-reduction counseling
The psycho-behavioral intervention includes administering questionnaires and monthly maintenance psychological support delivered via the Internet.
Sponsors
uBiome
Aurametrix
Mebo Research, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
* idiopathic malodor or PATM symptoms experienced over a period of several months or years * able to read and understand the study information * willing and able to comply with questionnaires, nutritional recommendations, and other study procedures
Exclusion criteria
* consistent inability to communicate and process things related to their symptoms * consistent inability to distinguish physical symptoms from pure emotional reactions * lack of motivation to start feeling better
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gut Microbiome | 1 year | Abundance \[operational taxonomic units\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life [Score] | 1 year | QoL: Scores range from 20 (lowest level of satisfaction with life) to 150 (maximal life satisfaction). Quality of life (QOL) will be measured with MEBO quality of life assessment questionnaire, a new tool designed on the basis of the Halitosis Associated Life-quality Test (HALT), Dermatology Life Quality Index (DLQI) and WHOQOL-100 questionnaires. Most questions were devised with a Likert scale of 0-5 where a higher score indicated a higher quality of life. Scores for five negatively framed questions are transformed to positively framed questions. Total QOL score (minimum score of 20 and maximum score of 150) is computed based on four aspects of QOL: physical health, psychological health, social support and environment. |
| Idiopathic Malodor Episodes | 1 year after study enrollment | The number of flareups after study enrollment |
| Change in Fecal Microbiome Composition Between Flare-ups and Improvements | 1 year | The fecal microbial composition will be measured via taxonomic profiling using 16S ribosomal RNA gene amplicon sequencing of submitted gut samples |
| Alpha Diversity | 1 year | Alpha (within-sample) diversity measure using microbial abundance information in a phylogenetic framework. Represented by abundance-weighted phylogenetic entropy. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MEBO/PATM Cohort The cohort is 119 individuals who experienced symptoms of idiopathic malodor (MEBO: 70 participants) and/or PATM (people allergic to me condition: 39 participants) | 119 |
| Non-MEBO/PATM Cohort 6 data volunteers that never experienced episodes of uncontrollable socially debilitating odor or PATM. | 6 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 39 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | MEBO/PATM Cohort | Non-MEBO/PATM Cohort | Total |
|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 12 | 40 years STANDARD_DEVIATION 20 | 40 years STANDARD_DEVIATION 13 |
| PATM status MEBO | 59 Participants | 0 Participants | 59 Participants |
| PATM status neither MEBO nor PATM | 0 Participants | 6 Participants | 6 Participants |
| PATM status PATM with or without MEBO | 60 Participants | 0 Participants | 60 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Argentina | 4 participants | 0 participants | 4 participants |
| Region of Enrollment Brazil | 4 participants | 0 participants | 4 participants |
| Region of Enrollment Burkina Faso | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 5 participants | 0 participants | 5 participants |
| Region of Enrollment Colombia | 1 participants | 0 participants | 1 participants |
| Region of Enrollment France | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Hong Kong | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Kenya | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Mexico | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Morocco | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Netherlands | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Nigeria | 3 participants | 0 participants | 3 participants |
| Region of Enrollment Pakistan | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Peru | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Philippines | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Portugal | 1 participants | 0 participants | 1 participants |
| Region of Enrollment South Africa | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Spain | 5 participants | 1 participants | 6 participants |
| Region of Enrollment Sweden | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United Kingdom | 10 participants | 0 participants | 10 participants |
| Region of Enrollment United States | 70 participants | 5 participants | 75 participants |
| Sex: Female, Male Female | 79 Participants | 1 Participants | 80 Participants |
| Sex: Female, Male Male | 40 Participants | 5 Participants | 45 Participants |
| TMAU status Negative TMAU test result | 26 Participants | 0 Participants | 26 Participants |
| TMAU status Not tested for TMAU | 58 Participants | 6 Participants | 64 Participants |
| TMAU status Primary TMAU | 23 Participants | 0 Participants | 23 Participants |
| TMAU status Secondary TMAU | 12 Participants | 0 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 125 |
| other Total, other adverse events | 0 / 125 |
| serious Total, serious adverse events | 0 / 125 |
Outcome results
Primary
Gut Microbiome
Abundance \[operational taxonomic units\]
Time frame: 1 year
Population: Study volunteers that submitted gut microbiome samples (84 out of 125 enrolled)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MEBO/PATM Cohort That Submitted Gut Samples | Gut Microbiome | Phylum Bacteroidetes | 25 Normalized OTU counts |
| MEBO/PATM Cohort That Submitted Gut Samples | Gut Microbiome | Phylum Actinobacteria | 3.73 Normalized OTU counts |
| MEBO/PATM Cohort That Submitted Gut Samples | Gut Microbiome | Phylum Tenericutes | 0.04 Normalized OTU counts |
| MEBO/PATM Cohort That Submitted Gut Samples | Gut Microbiome | Phylum Proteobacteria | 4.64 Normalized OTU counts |
| MEBO/PATM Cohort That Submitted Gut Samples | Gut Microbiome | Phylum Firmicutes | 52 Normalized OTU counts |
| Non-MEBO/PATM Cohort | Gut Microbiome | Phylum Proteobacteria | 3.70 Normalized OTU counts |
| Non-MEBO/PATM Cohort | Gut Microbiome | Phylum Firmicutes | 64 Normalized OTU counts |
| Non-MEBO/PATM Cohort | Gut Microbiome | Phylum Bacteroidetes | 33 Normalized OTU counts |
| Non-MEBO/PATM Cohort | Gut Microbiome | Phylum Tenericutes | 0.35 Normalized OTU counts |
| Non-MEBO/PATM Cohort | Gut Microbiome | Phylum Actinobacteria | 3.37 Normalized OTU counts |
Secondary
Alpha Diversity
Alpha (within-sample) diversity measure using microbial abundance information in a phylogenetic framework. Represented by abundance-weighted phylogenetic entropy.
Time frame: 1 year
Population: Participants that submitted valid stool samples. Since 16 individuals who observed improvement of their symptoms changed the status of their MEBO/PATM condition from active to remission/regression, their samples were grouped in two subgroups (38+33+23+6 = 84+16) Units analyzed represents samples submitted, 233 total.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEBO/PATM Cohort That Submitted Gut Samples | Alpha Diversity | 1.7 unitless |
| Non-MEBO/PATM Cohort | Alpha Diversity | 1.6 unitless |
| Subjects in Regression or Remission | Alpha Diversity | 1.7 unitless |
| Non MEBO/PATM Cohort | Alpha Diversity | 1.9 unitless |
Secondary
Change in Fecal Microbiome Composition Between Flare-ups and Improvements
The fecal microbial composition will be measured via taxonomic profiling using 16S ribosomal RNA gene amplicon sequencing of submitted gut samples
Time frame: 1 year
Population: Study participants that submitted two or more microbiome samples (each accompanied by answers to QoL questionnaire) and observed improvement of their symptoms (22 participants that documented their improvement out of 119 participants in MEBO/PATM cohort).~Participants from Non-MEBO Cohort are not included since they did not participate in the intervention; there was no difference between their entries in terms of flareups or improvements of MEBO/PATM conditions.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MEBO/PATM Cohort That Submitted Gut Samples | Change in Fecal Microbiome Composition Between Flare-ups and Improvements | Selected dermatological bacteria, normalized counts | 162 Normalized OTU counts in gut sample |
| MEBO/PATM Cohort That Submitted Gut Samples | Change in Fecal Microbiome Composition Between Flare-ups and Improvements | Corynebacteriales order, normalized counts | 302 Normalized OTU counts in gut sample |
| Non-MEBO/PATM Cohort | Change in Fecal Microbiome Composition Between Flare-ups and Improvements | Selected dermatological bacteria, normalized counts | 15 Normalized OTU counts in gut sample |
| Non-MEBO/PATM Cohort | Change in Fecal Microbiome Composition Between Flare-ups and Improvements | Corynebacteriales order, normalized counts | 91 Normalized OTU counts in gut sample |
p-value: 0.0295% CI: [26, 163]Wilcoxon (Mann-Whitney)
Secondary
Idiopathic Malodor Episodes
The number of flareups after study enrollment
Time frame: 1 year after study enrollment
Population: Individuals from MEBO/PATM cohort who submitted at least one gut microbiome sample accompanied by a QoL survey. Non-MEBO Cohort is not included since they never experienced MEBO/PATM flareups.
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| MEBO/PATM Cohort That Submitted Gut Samples | Idiopathic Malodor Episodes | severe flareups | 81 observations |
| MEBO/PATM Cohort That Submitted Gut Samples | Idiopathic Malodor Episodes | moderate flareups | 27 observations |
| MEBO/PATM Cohort That Submitted Gut Samples | Idiopathic Malodor Episodes | remission episodes | 6 observations |
| MEBO/PATM Cohort That Submitted Gut Samples | Idiopathic Malodor Episodes | not sure | 40 observations |
| Non-MEBO/PATM Cohort | Idiopathic Malodor Episodes | not sure | 3 observations |
| Non-MEBO/PATM Cohort | Idiopathic Malodor Episodes | severe flareups | 7 observations |
| Non-MEBO/PATM Cohort | Idiopathic Malodor Episodes | remission episodes | 12 observations |
| Non-MEBO/PATM Cohort | Idiopathic Malodor Episodes | moderate flareups | 12 observations |
Secondary
Quality of Life [Score]
QoL: Scores range from 20 (lowest level of satisfaction with life) to 150 (maximal life satisfaction). Quality of life (QOL) will be measured with MEBO quality of life assessment questionnaire, a new tool designed on the basis of the Halitosis Associated Life-quality Test (HALT), Dermatology Life Quality Index (DLQI) and WHOQOL-100 questionnaires. Most questions were devised with a Likert scale of 0-5 where a higher score indicated a higher quality of life. Scores for five negatively framed questions are transformed to positively framed questions. Total QOL score (minimum score of 20 and maximum score of 150) is computed based on four aspects of QOL: physical health, psychological health, social support and environment.
Time frame: 1 year
Population: Study participants from MEBO/PATM cohort that answered QoL survey (71 out of 119 in MEBO/PATM cohort). Since QOL questionnaire was administered multiple times for each participant, type of units analyzed is number of QoL submissions. Non MEBO/PATM cohort did not participate in this intervention.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MEBO/PATM Cohort That Submitted Gut Samples | Quality of Life [Score] | 57 score on a scale |
| Non-MEBO/PATM Cohort | Quality of Life [Score] | 97 score on a scale |