Exploring the Potential of Bioactive Textiles

The advancements in textile technology led to fabrics that not only clothe us but also promote a healthier and safer lifestyle. From antimicrobial and antioxidant properties to anti-inflammatory and anti-odor capabilities, along with protection against ultraviolet (UV) radiation and repelling unwanted elements, these textiles are setting a new standard for comfort, protection, and style. 

In an upcoming paper set to appear in the European Journal of Pharmaceutics and Biopharmaceutics (online ahead of print), the impact of bioactive textiles on human skin microbiota is extensively reviewed. 

The paper highlights the growing recognition that textile materials have a profound impact on the microorganisms present on the skin, leading to issues such as biological degradation, loss of strength, elongation, discoloration, and unpleasant odors (see Van Herreweghen et al). The emergence of "maskne," a form of mechanical acne resulting from continuous textile-skin adherence, further underscores the significance of this impact, causing dysbiosis in the skin microbiota and the growth of specific disease-associated species. 

Additionally, clothing textiles can act as carriers of microorganisms, posing risks of cross-infection, disease transmission, allergies, and malodors among individuals (reviewed in this paper). To address these challenges posed by microbial growth on textiles, the textile industry has made the search for new bioactive molecules with antimicrobial properties a top priority.

While functional textiles offer promising solutions, further research is needed to fully understand their environmental impact. To enhance the functionality of textiles and mitigate harm, the use of natural dyes derived from herbs, such as black cherry stems and hops flowers, is being explored. This approach not only improves functionality but also aligns with eco-friendly practices. Achieving the full potential of bioactive textiles requires interdisciplinary collaboration, bringing together expertise from various fields to develop safe and effective products that promote human health and safety.

REFERENCES

Suellen Ferro de Oliveira C, Kekhasharú Tavaria F. The impact of bioactive textiles on human skin microbiota. Eur J Pharm Biopharm. 2023 May 12:S0939-6411(23)00118-2. doi: 10.1016/j.ejpb.2023.05.004. Epub ahead of print. PMID: 37182552.

Van Herreweghen F, Amberg C, Marques R, Callewaert C. Biological and chemical processes that lead to textile malodour development. Microorganisms. 2020 Oct 31;8(11):1709.

Gulati R, Sharma S, Sharma RK. Antimicrobial textile: recent developments and functional perspective. Polymer Bulletin. 2022 Aug;79(8):14346-14364, DOI: 10.1080/15440478.2022.2064391

Olfactory Signatures and COVID-19

Olfactory disorders have a significant impact on human lives - be it a lost/distorted sense of smell or unpleasant odors affecting the sense of smell of others. 

Odortypes can be influenced by human leukocyte antigen (HLA) genes of the major histocompatibility complex (MHC), genes associated with stronger response to COVID-19 vaccine as well as the severity of this disease. HLA may also be related to people's perception of the odor of other people. 

Of course, these are not the only variables involved, and there are more potentially overlapping risk factors for olfaction, metabolic body odor (MEBO), including trimethylaminuria (TMAU), and COVID-19: FMO3, SELENBP1, HspA, UGT2A1/UGT2A2, etc. 

A new peer-reviewed paper reporting results of a decentralized observational study (NCT04832932) compared MEBO participants to general populations in respect to their response to COVID-19 vaccines and SARS-Co-V2 infections. 

Body odor flareups were observed in about 10% of malodor sufferers after vaccination, as preliminarily reported. This number was similar to flareups of other chronic symptoms in groups of participants with gastrointestinal and autoimmune disorders.  

Long-term worsening of body odor was observed by other researchers after COVID-19 vaccination in about ~1% of studied populations. Dry mouth leading to halitosis was 10 times more prevalent compared to flu vaccines. MEBO participants reported stronger reactions than general population pointing to genetic and microbiome influences beyond FMO3.  

A better understanding of systemic malodor conditions could offer leads for targeted therapies. Findings on genetic and microbiome overlaps between COVID-19 and MEBO could pave the way for precision medicine to address the unmet needs of odor sufferers.

REFERENCE

Gabashvili IS. The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups. JMIR Formative Research. 2022 Nov;6(11):e41914. DOI: 10.2196/41914. PMID: 36309347; PMCID: PMC9640199.

On Cabbage and Selenium Binding Protein 1

Mutations in the gene encoding Selenium Binding Protein (SELENBP1) on chromosome 1q21 were found in multiple individuals with extra-oral halitosis. These individuals had increased levels of methanethiol and dimethylsulfide in their breath perceived as unpleasantly cabbage-smelling. It was reported to worsen after drinking beer. 

The mutations responsible include rs1553204817 (OMIM: 604188.0001: c.1039G>T); rs758495626 (c.673G>T (p.Gly225Trp)), rs1357490520 (c.481+1G>A disrupting splice site), and rs1553204840 (c.985C>T)

SELENBP1 was identified as a methanethiol oxidase (MTO), catalyzing the conversion of methanethiol (H3C-SH) to hydrogen sulfide (H2S), hydrogen peroxide (H2O2) and formaldehyde (HCHO). If this enzyme is not properly functional, the body will be releasing more Methanethiol  - a volatile and toxic gas with the characteristic smell of rotten cabbage. We get this compound from food - not only the cancer-fighting cabbage family, including radishes, but also orange juice, pineapple, strawberries, asparagus, wheat bread, gruyere cheese, coffee, roasted filberts and even cooked rice. Water, cherries, apples, whole milk, spinach and citrusy fruits could counteract the odor in some individuals. 

Selenium binding protein1 (SELENBP1) has been also associated with a rare disease hypermethioninemia (sometimes accompanied by learning disabilities and neurological problems), several cancers and schizophrenia (downregulated at its onset and upregulated at later stages); hypertension and ischemic heart conditions. Dysregulation of SELENBP1 is common to Zika virus (ZIKV) and dengue infections, and Guillain-Barré syndrome. It was also found to COVID-19.

REFERENCES

Pol A, Renkema GH, Tangerman A, Winkel EG, Engelke UF, De Brouwer AP, Lloyd KC, Araiza RS, Van Den Heuvel L, Omran H, Olbrich H. Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature genetics. 2018 Jan;50(1):120-9.

Philipp TM, Will A, Richter H, Winterhalter PR, Pohnert G, Steinbrenner H, Klotz LO. A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes. Redox Biology. 2021 Jul 1;43:101972.

Lin X, Lin Z, Zhao X, Liu Z, Xu C, Yu B, Gao P, Wang Z, Ge J, Shen Y, Li L. Serum SELENBP1 and VCL Are Effective Biomarkers for Clinical and Forensic Diagnosis of Coronary Artery Spasm. International Journal of Molecular Sciences. 2022 Oct 31;23(21):13266.

Chau EJ, Mostaid MS, Cropley V, McGorry P, Pantelis C, Bousman CA, Everall IP. Downregulation of plasma SELENBP1 protein in patients with recent-onset schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018 Jul 13;85:1-6.

Zhang X, Hong R, Bei L, Hu Z, Yang X, Song T, Chen L, Meng H, Niu G, Ke C. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition. Open Medicine. 2022 Jan 1;17(1):1390-404.

Moni MA, Lio’ P. Genetic profiling and comorbidities of zika infection. The Journal of infectious diseases. 2017 Sep 15;216(6):703-12.

de Melo CV, Bhuiyan MA, Gatua WN, Kanyerezi S, Uzairue L, Abechi P, Kumar K, Rahmat J, Giwa A, Mwandira G, Olamilekan AM. Transcriptomic dysregulations associated with SARS-CoV-2 infection in human nasopharyngeal and peripheral blood mononuclear cells. bioRxiv. 2020 Jan 1.

Albert-Puleo M. Physiological effects of cabbage with reference to its potential as a dietary cancer-inhibitor and its use in ancient medicine. Journal of ethnopharmacology. 1983 Dec 1;9(2-3):261-72.

Rebuild your Health

There is increasing evidence that intestinal microbial dysbiosis has a role in the pathogenesis of systemic malodor conditions and other metabolic disorders. The most studied non-syndromic malodor condition Trimethylaminuria is usually inherited in an autosomal recessive fashion, which means that two mutations from both parents, both affecting abilities of FMO3 enzyme to catalyze the N-oxidation of trimethylamine into trimethylamine (eg, [Glu158Lys (rs2266782) and Glu308Gly (rs2266780)]), may be needed for a person to have symptoms. Yet genotype is not always predictive of phenotype, not even in this case.

Illustration by Monica Garwood

Studies have shown that the symptoms of metabolic inefficiencies, food intolerance and even allergies can be relieved by changing the composition of intestinal microbes and adjusting dietary components feeding these microbes - to encourage growth of microorganisms properly digesting problem ingredients. Lactose-digesting bacteria Lactobacillus acidophilus, Lactobacillus bulgaricus and Streptococcus thermophilus, for example, can help to digest lactose into useful compounds, instead of offensive gas. On the other hand, the low-FODMAP diet reduces gastrointestinal symptoms by reducing the food that bacteria ferment. For lactose-intolerance, however,  the "O" in FODMAPs - oligosacharides - can be beneficial as Galacto-oligosaccharides (GOS) are useful prebiotics promoting the growth of the right microorganisms. 

Rebuilding the network of microorganisms on and inside our bodies can help to improve the volatiles in the surrounding air, aka body and breath odor. Microbes associated with unpleasant odors include Anaerococcus, Corynebacterium, Campylobacter, and Propionibacterium [1], Gardnerella, Alloprevotella, Sutterella, and species of Candida. Microbes associated with improvements in odors include archaebiotic Methanomassiliicoccus luminyensis, Lactobacillus pentosus KCA1, and Lactobacillus salivarius, but there are more, working together and relying on each other. Our studies (see protocols of microbiome [2] and volatilome [3] trials published on Medrxiv)  identified several microbial strains and volatile compounds associated with improvement of malodor symptoms. We are currently summarizing our results and plan to publish it. Development of personalized protocols and defining the right compositions of probiotics and prebiotics is a long-term research endeavor. Meanwhile, be your own best medical researcher and take control of your wellbeing: 

Step 1: Pull out your fitness journal and create an action plan

• Analyze your diet, everyday activities, exercise and sleep patterns to make initial guesses about things that could be triggering your flareups or making you feel better. Write out a list of these things. 
• Break your goal into small steps and milestones. For example: if you have fructose as a potential trigger on your list, go fructose free for a week. An earlier survey of about 100 body odor and halitosis sufferers indicated stress (34%), food (25%) and environment, including the weather and perfumed products (15%) as main triggers of odors or PATM. Make sure you are not missing something in your diet - like Zinc, Vitamin C, or Vitamin D - insufficient amounts of these vitamins and minerals could also contribute to PATM. 
• Develop metrics for evaluating progress. Some people can't objectively evaluate their malodor or PATM condition. Try to find a trust buddy or take note of how the people around you react when you’re in close proximity. For example, pay attention to the space people leave between you and themselves (assuming COVID-19 is behind us and the 6-feet rule no longer applies!)

Step 2: Change your diet, physical activity and behavior

• Intestinal lining is regenerating every five to seven days, so you need to stick to your diet for at least a week to notice improvements in your symptoms. Most elimination diets are actually recommended for about 3–6 weeks, to allow the antibodies (negatively reacting to problem food components) dissipate. So if your diet seems to be helping, extend it to 3 or 6 weeks. 
• If it is not helping, try the next thing on your list. It should not be just diet - one study showed that bad breath was associated with abnormal sleep patterns. Perhaps you need to reevaluate your clothing material, temperature an humidity or mycotoxins in the environment? Are you getting enough sunlight ? Does your home have a healthy microbiome? Try to eliminate the triggers one at a time. No need to reduce your overall food intake, many people observe malodor or PATM flareups when they are hungry & undernourished. Try to train your body to digest more fiber - but start adding them to your diet little at a time, on weekends when you can safely experiment.   

Step 3: Let go of past hurts

• Stop dwelling on the past. You have the power to change your future. Learn how to express confidence with your body language. Pretend you are comfortable in presence of other people and they will learn to be comfortable in yours. 

RFRERENCES

1. Gabashvili IS. Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights From a Virtually Conducted Clinical Trial. JMIR Dermatology. 2020 Nov 4;3(1):e10508.

2. Gabashvili I.S. Dynamics of the Gut Microbiota in MEBO and PATM conditions: Protocol of a fully remote clinical study. medRxiv. 2020 Aug.24. medRxiv 2020.08.21.20179242; doi: https://doi.org/10.1101/2020.08.21.20179242

3. Gabashvili I.S. Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study medRxiv 2021, Jan. 26 2021.01.25.21250101; doi: https://doi.org/10.1101/2021.01.25.21250101

Microbial diagnostics of MEBO

There are many medical conditions for which there are no standard tests for definite diagnosis and no established cures.  Diagnosing and curing Metabolic Body Odor (MEBO) is even more difficult. Especially because MEBO is an umbrella term for several different conditions.

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Gender - confounder of concern?

Background and clinical characteristics measured at baseline are comparable in the groups of our study. But this doesn't eliminate the need to investigate the impact of confounding. We've already analyzed the effects of age, What about gender as a potential confounder?

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Age and Metabolic Body Odor

MEBO is a complex condition and while some of the cases seem simpler, non-linear analysis approaches are better equipped to handle the task.  And this creates new challenges regarding  the existence of confounding factors.

Reducing the stigma of odor disorders

Some conditions - such as obesity, depression and functional odor disorders - come with a social stigma. Understanding the etiology of these conditions helps to avoid stereotypes and find remedies. 

Metabolomics analysis of morning urine samples helped to evaluate the heterogeneity of MEBO population as good as challenge tests, procedures used to induce symptoms and assess resilience to perturbations caused by sugars. 


...  Read more ... 

On what's in your head, the downside of diversity and deodorizing bacteria: preliminary results of NCT03582826

Mirrored from Aurametrix, preliminary results of NCT03582826:

By now, 105 uBiome kits were registered in our Quality of Life form (out of 300+ sets sent). 16 volunteers have submitted all 3 samples and 23 registered one or two kits. Over half of our participants have not yet started the study. We hope that this post will answer some of their questions on where to start.

The goal of MEBO Gut Microbiome study is to identify microbial communities associated with flare ups and remission of systematic malodor or PATM conditions.  Participants are asked to answer MEBO Quality of Life (QoL) questionnaire about the last 24 hrs before every sample is taken. The Questionnaire is embedded into English and Spanish posts about the study.  The answers are used to calculate total QoL score that increases with less odor and more wellbeing. The questionnaire evaluates physical health, psychological health, social support and environment such as diet and exercise. A separate score is calculated for MEBO (malodor/PATM) symptoms.

This post is about preliminary results of the first 41 uBiome kits representing samples from 24 participants. Quality of Life scores varied from 55 to 149 (best, "ideal" quality of life would be 150), while MEBO scores ranged from 3 (experienced MEBO/PATM symptoms "all the time" and odor was lingering for hours at 10 feet and farther) to 25 (100% odor free).

The pie chart on the right shows social environment for MEBO volunteers: almost half of study participants had active social lives interacting with over 8 people per day. Almost 20% of social interactions were entirely positive, while 10% were entirely negative. Social support did not correlate with MEBO symptoms and it was not predictor nor protective of malodor.

Graphs of depressive feelings vs odors is another prove that even with stress as a trigger, body odors are not all in your head. Obviously, those free of malodors tend to be happier, but it's possible to control depression even with worst MEBO symptoms and happy mood, alone, does not help to control the symptoms.

uBiome provides a multitude of measurements characterizing gut microbiomes. One of the most widely used metrics is gut diversity metrics.

Microbial diversity is cornerstone of a good health and decreased diversity is likely to be associated with poor wellbeing including malodors. Our data, however, show that most MEBO volunteers have healthy diversity scores that do not correlate with incidence of odors. Correlation is observed only for  cases of very low, unhealthy diversity, especially for total quality of life scores as opposed to just malodor symptoms. Even more so, MEBO volunteers in remission, completely free of odors, had healthy,  but not the very best diversity scores.

In extremely diverse communities, people may be less inclined to trust each other, vote and volunteer for activities. In people not suffering from uncontrollable odors, microbes and hosts have a balanced dialogue, and form symbiotic relationships beneficial for both parties.

Could it be that MEBO sufferers have more "smelly" bacteria and less bacteria neutralizing the smell?  Levels of traditional probiotic strains in the study participants do not seem to correlate with their odor levels. As more data is accumulated, interesting patterns are emerging for less common bacteria. An example is Anaerovorax, bacterium that processes putrid-smelling compounds produced by clostridia, pseudomonads, lactic acid and other bacteria from amino acids in food. Anaerovorax is observed in only 3% of uBiome samples, but it is present in a quarter of MEBO participants. Plotting its levels in all samples with Anaerovorax present against the scores representing improvement of MEBO symptoms (from worst odor to no odor), shows a clear trendline - the more Anaerovorax, the less odor. We note that this seem to be the case for ONLY a subset of study participants. For example, participants #901298 and #901240 who contributed 2 samples each into the first 41-sample-set, had 0 Anaerovorax on their worse day and over 0.03% Anaerovorax on their better days. # 901240 submitted 2 "bad day" samples (which is perfectly fine - as it still yielded much needed data!) had a little more Anaerovorax on a slightly better day. #90346 had experienced exactly the same MEBO symptoms on both days of sampling, but the result with 0 Anaerovorax corresponded to a worse Quality of Life score. #90365 experienced exactly the same symptoms for days with and without Anaerovorax, and had the same Quality of Life Score, but there was a noticeable difference in diet. This person had more Anaerovorax when consumed more odor triggers in food (onions and vinegar).

There is not much known about the role of Anaerovorax in human gut. It is proposed to increase when adding meat to a usually vegetarian diet and with increased fasting insulin levels. It is also increased in healthy preadolescent children (7 to 12 years old) and by minerals such as Zinc and Manganese.

Levels of TMA-producing bacteria such as Desulfibrio and Bacteroides seem to lower when odor levels are decreasing in most cases, although signal-to-noise ratio is weak and the dependence is very individual (see Figure). The trend is similar for #901214, #90265, #900841 and #901273. #901253 is one of the outliers: MEBO symptoms in this case were improving with higher levels of Bacteroides and lover diversity (and a much stricter diet).

Bacteroides maintain a complex and generally beneficial relationship with the host. The genus Bacteroides makes up to 30% of the bacteria in the human gut. Levels of Bacteroides increase with rapid weight loss. Specific species of Bacteroides, have a role in preventing infection with Clostridium difficile. Level of Bacteroides, however, increase (or significantly decrease) in inflammatory bowel disease and chronic fatigue syndrome.
Lactobacillus and bifidobacteria probiotics, garlic, walnuts and barley could all decrease levels of Bacteroides. Polydextrose (dietary fiber found in traditional bakery items, beverages, dairy products and sauces) not only decreases Bacteroides but also increases probiotic strains of Lactobacillus and Bifidobacterium.

These are only preliminary results. We'll be looking at more complex patterns in bacterial community structures associated with different subgroups of study participants. We'll be posting new findings as we mine more data and get additional results.

If you have not started the study yet, we hope that this post encourages you to start participating. As you see, every data point counts, even if the results of your experimentation and odor reduction approaches are not as good as we wished.


REFERENCES


Vemuri R, Gundamaraju R, Shastri MD, Shukla SD, Kalpurath K, Ball M, Tristram S, Shankar EM, Ahuja K, Eri R. Gut Microbial Changes, Interactions, and Their Implications on Human Lifecycle: An Ageing Perspective. BioMed research international. 2018;2018.

Zhang Q, Xiao X, Li M, Yu M, Ping F, Zheng J, Wang T, Wang X. Vildagliptin increases butyrate-producing bacteria in the gut of diabetic rats. PloS one. 2017 Oct 16;12(10):e0184735.

Roeder J, Schink B. Syntrophic degradation of cadaverine by a defined methanogenic coculture. Applied and environmental microbiology. 2009 Jul 15;75(14):4821-8.

Lau SK, Teng JL, Chiu TH, Chan E, Tsang AK, Panagiotou G, Zhai SL, Woo PC. Differential Microbial Communities of Omnivorous and Herbivorous Cattle in Southern China. Computational and structural biotechnology journal. 2018 Jan 1;16:54-60.

Filocamo A, Nueno-Palop C, Bisignano C, Mandalari G, Narbad A. Effect of garlic powder on the growth of commensal bacteria from the gastrointestinal tract. Phytomedicine. 2012 Jun 15;19(8-9):707-11.

Cruden DL, Galask RP. Reduction of trimethylamine oxide to trimethylamine by Mobiluncus strains isolated from patients with bacterial vaginosis. Microbial Ecology in Health and Disease. 1988 Jan 1;1(2):95-100.

Craciun S, Balskus EP. Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme. Proceedings of the National Academy of Sciences. 2012 Dec 26;109(52):21307-12.

Research Consent for the ongoing MEBO Microbiome study

secure https sites:       MEBO Microbiome                Life Quality Test

Research study: Dynamics of the Gut Microbiota in Idiopathic Malodor Production

● Being in a study is voluntary – your choice.
● If you join this study, you can still stop at any time.
● No one can promise that a study will help you.
● Do not join this study unless all of your questions are answered.

Before you decide whether to participate in this research study, you should review:

1.     The purpose of the research study

2.     The study procedures

3.     How long your involvement in the research will last

4.     Any procedures that are experimental

5.     Any reasonably foreseeable risks, discomforts, and benefits of the research

6.     Any potentially beneficial alternative procedures or treatments

7.     How the confidentiality of your data will be maintained

8.     The possibility of unforeseeable risks

9.      Any added costs to you

10.     What happens if you decide to stop participating

11.     New findings that may affect your willingness to participate

12.     How many people will be in the study

Introduction

MEBO Research, Inc., (“MEBO”) is a sufferer-founded patient advocacy international campaign registered in the State of Florida, U.S., since April 21, 2010, under section 501(c)(3) of the Internal Revenue Code, classification of Public Charity. MEBO Research is also registered in England and Wales as a Not For Profit, Limited by Guarantee Company (2009). MEBO is a NORD and EURORDIS Organization Member and its directors are moderators of the Trimethylaminuria Community at RareConnect.org. MEBO is referenced as an Advocacy and Support Organization in websites like the Genetic Alliance and Orphanet.

MEBO means metabolic body odor and it includes systemic body odor, bad breath and continuing episodes of malodor NOT related to hygiene or excessive gas. PATM denotes "People Allergic To Me" condition.

PURPOSE OF RESEARCH

You are invited to participate in a research study of microbial dynamics in MEBO and PATM conditions.  We hope to learn what microbial communities are associated with flare ups and remissions of these conditions and best ways to reduce the symptoms. 

You were selected as a possible participant in this study because you demonstrated good communication skills and willingness to follow nutritionally balanced dietary regimes and contribute follow-up outcome data.

If you decide to terminate your participation in this study, you should notify Maria de la Torre at maria.delatorre@meboresearch.org 

This research study is looking for up to 100 people with all manifestations of body malodor, halitosis and/or PATM. We expect to enroll research study participants, throughout the United States and internationally.

VOLUNTARY PARTICIPATION

Your participation in this study is entirely voluntary. Your decision not to participate will not have any negative effect on you or your medical care. You can decide to participate now or withdraw your consent at any time throughout the study process without any loss of benefits or medical care to which you may be entitled, if any.

DURATION OF STUDY INVOLVEMENT

This research study is expected to take approximately one year.  

PROCEDURES

If you choose to participate, the Protocol Director, Irene Gabashvili, PhD, and her research study staff, Maria de la Torre will address all matters regarding this research process with you in writing via email to the email address you provide. Your formal reply to said communications will also need to be in writing via email.  In this manner, clear instructions, charts, graphs, results, calendar, and your feedback will be presented in an orderly manner. 

None of the surveys or other procedures used by the investigators in this Research study are invasive or experimental. The procedures involved do not involve significant risks, and no compensation or treatment is available if injury occurs as a result of participation. Swabs and other materials used for sample collection are sterilized prior to shipment and must be handled with proper care and hygiene. Should you be uncomfortable handling the collection kit and accepting responsibility for its use, please reconsider your participation in this study.

We are asking you to self-sample with three uBiome gut microbiome kits and fill in this questionnaire:

These charts describe when you could collect the three samples depending if your condition is in active state or in remission:

When you are ready to begin sampling, follow the instructions below to collect your sample:

You may also want to answer uBiome questions about your stool type, symptoms and wellbeing. 
  
After you return your sample via the prepaid mailer, your uBiome Explorer test report will be available via your patient portal approximately 6 weeks later. You will also receive an email notifying you that your results are ready.



Any of your samples which are used in research may result in new products, tests or discoveries. In some instances, these may have potential commercial value and may be developed and owned by uBiome or others. Our agreement with Ubiome allows them to file any patents relating to test results. However, donors of samples do not retain any property rights to the materials.  Therefore, you would not share in any financial benefits from these products, tests or discoveries.

The results of the study of your samples from this project will be used for research purposes only. Regarding informing you of the test results, you should understand the following:

·       The information may be too limited to give you particular details or consequences;

Information from analyses of your coded samples and your coded medical information will be put into one of the National Institutes of Health (NIH) databases along with information from the other research participants and will be used for future research. These databases will be accessible by the Internet. Only anonymous information from the analyses will be put in a completely public database, available to anyone on the Internet.

No traditionally-used identifying information about you, such as your name, address, telephone number, or social security number, will be put into the public database. While the public database will not contain information that is traditionally used to identify you, people may develop ways in the future that would allow someone to link your medical information in our databases back to you. For example, someone could compare information in our databases with information from you (or a blood relative) in another database and be able to identify you (or your blood relative). It also is possible that there could be violations to the security of the computer systems used to store the codes linking your genetic and medical information to you.

However, your privacy is very important to us and we will use safety measures to protect it. Despite all of the safety measures that we will use, we cannot guarantee that your identity will never become known.

PARTICIPANT RESPONSIBILITIES

As a participant, your responsibilities include: 

·       Follow the instructions of the Protocol Director and study staff.

·       Tell the Protocol Director or research study staff about any side effects, doctor visits, or hospitalizations that you may have.

·       Keep your diaries as instructed.

·       Complete your questionnaires as instructed.

·       Ask questions as you think of them.

·       Tell the Protocol Director or research staff if you change your mind about staying in the study.
·       Destroy or return any unused tests kits to uBiome.  

WITHDRAWAL FROM STUDY

If you first agree to participate and then you change your mind, you are free to withdraw your consent and discontinue your participation at any time.  Your decision will not affect your ability to receive medical care for your disease and you will not lose any benefits to which you would otherwise be entitled.

If you decide to withdraw your consent to participate in this study, you should notify Maria de la Torre at maria.delatorre@meboresearch.org. 

You should destroy or return any unused test kits or other materials to uBiome at the completion or earlier termination of this study

POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES

There are risks, discomforts, and inconveniences associated with any research study.  These deserve careful thought.  You should talk with the Protocol Director if you have any questions.

• Some survey questions may make you or your family members uncomfortable. 

• Your data, survey responses, and/or personally identifying information may be compromised in the event of a security breach or failure to follow protocol. In the event of such a breach, if your data are associated with your identity, they may be made public and it may have social and psychological consequences for you or your loved ones. 

• When investigators publish results from this study, your information may be included within pooled summaries that are made public. Identification of your individual-level data from those summaries would be extremely difficult, but it is possible that a third party that has obtained partial data from you could compare their partial data to the published results and indirectly determine some of your survey responses. 

• While the information we keep will not include names, and the microbiome is not uniquely identifiable, human genetic information is unique and can be used to identify people by linking or tracing DNA in public databases. 

• As with any online service, if you disclose your account password to others, they may be able to access your account and your information. There may be additional risks to participation that are currently unforeseeable.

POTENTIAL BENEFITS

We cannot and do not guarantee or promise that you will receive any benefits from this study.

ALTERNATIVES

The alternative is not to participate in this study.

PARTICIPANT’S RIGHTS

You should not feel obligated to agree to participate.  Your questions should be answered clearly and to your satisfaction.  If you decide not to participate, tell the Protocol Director. 

You will be told of any important new information that is learned during the course of this research study, which might affect your condition or your willingness to continue participation in this study.

ClinicalTrials.gov

 A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law.  This Web site will not include information that can identify you.  At most, the Web site will include a summary of the results.  You can search this Web site at any time.

https://clinicaltrials.gov/ct2/show/NCT03582826

CONFIDENTIALITY

The results of this research study may be presented at scientific or medical meetings or published in scientific journals.  Your identity and/or your personal health information will not be disclosed except as authorized by you or as required by law.  However, there is always some risk that even de-identified information might be re-identified.

Patient information may be provided to Federal and other regulatory agencies as required.  The Food and Drug Administration (FDA), for example, may inspect research records and learn your identity if this study falls within its jurisdiction.

Authorization To Use Your Health Information For Research Purposes 

Because information about you and your health is personal and private, it generally cannot be used in this research study without your written authorization.  If you sign this form, it will provide that authorization.  The form is intended to inform you about how your health information will be used or disclosed in the study.  Your information will only be used in accordance with this authorization form and the informed consent form and as required or allowed by law.  Please read it carefully before signing it. 

What is the purpose of this research study and how will my health information be utilized in the study?

The purpose of this study is to learn what microbial communities are associated with flare ups and remissions of malodor and PATM conditions. The information in some form will be submitted to the sponsor, uBiome. Your de-identified information may be included within pooled summaries when investigators publish results from this study. 

Do I have to sign this authorization form?

You do not have to sign this authorization form.  But if you do not, you will not be able to participate in this research study. Signing the form is not a condition for receiving any medical care outside the study.

If I sign, can I revoke it or withdraw from the research later?

If you decide to participate, you are free to withdraw your authorization regarding the use and disclosure of your health information (and to discontinue any other participation in the study) at any time.  After any revocation, your health information will no longer be used or disclosed in the study, except to the extent that the law allows us to continue using your information (e.g., necessary to maintain integrity of research).  If you wish to revoke your authorization for the research use or disclosure of your health information in this study, you must write to Irene Gabashvili at irene.gabashvili@meboresearch.org

What Personal Information Will Be Obtained, Used or Disclosed?

Your health information related to this study, may be used or disclosed in connection with this research study, including, but not limited to severity of your symptoms and laboratory test results. 

Who May Use or Disclose the Information?

The following parties are authorized to use and/or disclose your health information in connection with this research study:

·        The Protocol Director (Irene Gabashvili)

·        Research Staff (Maria de la Torre)

Who May Receive or Use the Information?

The parties listed in the preceding paragraph may disclose your health information to the following persons and organizations for their use in connection with this research study:

·        The Office for Human Research Protections in the U.S. Department of Health and Human Services

When will my authorization expire?

Your authorization for the use and/or disclosure of your health information will end on December 31, 2019 or when the research project ends, whichever is earlier.

Will access to my medical record be limited during the study?

To maintain the integrity of this research study, you may not have access to any health information developed as part of this study until it is completed.  At that point, you would have access to such health information if it was used to make a medical or billing decision about you (e.g., if included in your official medical record).

FINANCIAL CONSIDERATIONS

Payment/Reimbursement

You will not be paid to participate in this research study.

                                                                                

Costs

There is no cost to you for participating in this study, other than basic expenses like Internet usage and the personal time it will take to fill in the questionnaires.

International participants may be asked to donate to MEBO Research to partially compensate for shipping costs. 

Sponsor

uBiome and MEBO Research are providing financial support and/or material for this study. uBiome is supporting microbiome testing and partial analysis of the results, and domestic shipping costs. MEBO Research will be covering International shipping costs.

COMPENSATION for Research-Related Injury

All forms of medical diagnosis and treatment – whether routine or experimental – involve some risk of injury.  In spite of all precautions, you might develop medical complications from participating in this study.  If such complications arise, the Protocol Director and the research study staff will assist you in obtaining appropriate medical treatment.  In the event that you have an injury or illness that is directly caused by your participation in this study, reimbursement for all related costs of care first will be sought from your insurer, managed care plan, or other benefits program.  You will be responsible for any associated co-payments or deductibles as required by your insurance.

If costs of care related to such an injury are not covered by your insurer, managed care plan or other benefits program, you may be responsible for these costs.  If you are unable to pay for such costs, the Protocol Director will assist you in applying for supplemental benefits and explain how to apply for patient financial assistance from the hospital.

You do not waive any liability rights for personal injury by signing this form.

CONTACT INFORMATION

Questions, Concerns, or Complaints:  If you have any questions, concerns or complaints about this research study, its procedures, risks and benefits, or alternative courses of treatment, you should ask the Protocol Director.

Injury Notification:  If you feel you have been hurt by being a part of this study, please contact the Protocol Director or Research Staff.

Independent Contact:  If you are not satisfied with how this study is being conducted, or if you have any concerns, complaints, or general questions about the research or your rights as a participant, please contact the MEBO Institutional Review Board (IRB) to speak to someone independent of the research team at mike@meboresearch.org

Alternate Contact:  If you cannot reach the Protocol Director, please contact Maria de la Torre at maria.delatorre@meboresearch.org 

Questions, Concerns, or Complaints:  If you have any questions, concerns or complaints about this research study, its procedures, risks and benefits, or alternative courses of treatment, you should ask the Protocol Director, Irene Gabashvili at irene.gabashvili@meboresearch.org.  You should also contact her at any time if you feel you have been hurt by being a part of this study.

EXPERIMENTAL SUBJECT’S BILL OF RIGHTS

As a research participant you have the following rights.  These rights include but are not limited to the participant's right to:

• be informed of the nature and purpose of the experiment;
• be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized;
• be given a description of any attendant discomforts and risks reasonably to be expected;
• be given an explanation of any benefits to the subject reasonably to be expected, if applicable;
• be given a disclosure of any appropriate alternatives, drugs or devices that might be advantageous to the subject, their relative risks and benefits;
• be informed of the avenues of medical treatment, if any available to the subject after the experiment if complications should arise;
• be given an opportunity to ask questions concerning the experiment or the procedures involved;
• be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation without prejudice;
• be given a copy of the signed and dated consent form; and
• be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion or undue influence on the subject's decision.