Asian Bioethics Review (2017) 9:311–324

https://doi.org/10.1007/s41649-017-0033-9
O R I G I N A L PA P E R

Biobanking for human microbiome research: promise,

risks, and ethics

Yonghui Ma 1 & Hua Chen 2 & Ruipeng Lei 3 &

Jianlin Ren 4,5

Published online: 7 December 2017

# National University of Singapore and Springer Nature Singapore Pte Ltd. 2017

Abstract With the advancement of human microbiome research, it is inevitable that a

growing number of biobanks will include a collection of microbiota specimens to
characterize the microbial communities that inhabit the human body and explore the
relationships between the microbiota and their human hosts. Biobanks of human
microbiota and their associated genetic information may become a valuable health
resource. But, this area of research also presents ethical and social problems, some of
which are distinct from those faced by biobanks that store human tissue samples. This
paper examines four core issues which are considered highly relevant to microbiome
biobanking: the nature of human microbiome samples and how different understand-
ings have an impact on benefit/risk evaluation, privacy, informed consent, and
returning the result to participants. We argue that these issues should be addressed
early on in microbiome research projects and also call for adjusting or developing new
governance mechanism to better accommodate these changes.

Keywords Human microbiome research . Stool bank . Privacy . Informed consent . Risk .
Research ethics

* Yonghui Ma
yhma@xmu.edu.cn

1
Centre for Bioethics, Medical College, Xiamen University, Xiamen, China
2
School of Health Management, Guangzhou Medical University, Guangzhou, China
3
Centre for Bioethics, Department of Philosophy, School of Humanities, Huazhong University of
Science and Technology, Wuhan, China
4
Institute for Human Microbiome Research, Medical College, Xiamen University, Xiamen, China
5
Department of Digestive Diseases, Zhongshan Hospital affiliated to Xiamen University, Xiamen,
China
312 Asian Bioethics Review (2017) 9:311–324

Introduction

Due to the advent of high-throughput molecular techniques, scientific knowledge about

the human microbiome in recent years is exploding in an unprecedented and transfor-
mative way. Research in this area promoted a dramatic increase in our ability to study the
microorganism communities in the human body and environment. The application of
new knowledge generated from microbiome research could be revolutionary and have a
wider implication ranging from healthcare services to people’s conceptions of health and
disease, and to the mass production and distribution of commercial products promising
health benefits and disease prevention (e.g., probiotics and prebiotics). This work,
similar to more familiar human genome research, relies heavily on the use of biobanks.
Biobanks, also known as biorepositories, are defined as large collections of biolog-
ical specimens and tissue samples, and associated medical and clinical information used
for research purposes. With the increasingly widespread use of stored samples in
research in the past few decades, biobanks are now playing an increasingly important
role in biomedical research (National Bioethics Advisory Commission 1999). Mean-
while, ethical and social issues generated by biobanks have also been recognized and
discussed. However, most discussions on these issues in bioethics and social sciences
are focused on the implications of biobanks storing human tissues. Due to the symbi-
otic relationship of the human microbiome with the host, biobanking on human
microbiome samples has the potential to raise new ethical challenges and add further
complications to debates on the ethical, legal, and social issues (ELSI) of biobanking.
This area demands investigation into social and ethical implications of research on
human microbiome and biobanking. However, literature on this area is insufficient.
This paper will first provide an overview of the current human microbiome research
and describe the types, functions, and activities of biobanking for human microbiome.
We then identify some of the ethical challenges that confront microbiome biobanks and
in particular examine four core issues which are considered highly associated with
microbiome biobank: nature and characterization of human microbiome samples and
how different understandings have an impact on benefit/risk evaluation, privacy,
informed consent, and returning the result to participants. We will also argue that the
existing regulations that govern human subject research cannot be applied to human
microbiome biobanks and provide suggestions on how to develop effective regulations
to better governance of microbiome biobanks.

Overview of Human Microbiome Research

Traditionally, most of us hold the Bcommon knowledge^ that all bacteria are harmful
and should be eliminated; we wash hands, use various hygiene products claiming to
Bkill 99.9% of all bacteria,^ and hope to live in a super-clean environment to reduce the
possibilities of pathogen infection. However, until recently, we did not realize that most
bacteria are Bfriendly^ to us, not Benemies,^ and that with over-consumption of
antimicrobial products, we are actually harming ourselves.
The term human microbiome refers to the population of microorganisms, including
bacteria, viruses, fungi, and protozoans, and their genetic material that live on and
inside the human organisms (Honey 2008). It is often presented as common knowledge
Asian Bioethics Review (2017) 9:311–324 313

that in and on our bodies, microbial cells outnumber human cells by a factor of 10 to 1.
However, a recent study shows that the ratio is much closer to 1:1 and their total mass is
about 0.2 kg (Sender et al. 2016). The number of bacteria occupying the human body is
estimated to be in the trillions and it is estimated that there are two to four million
distinct nonhuman genes in the human body (Rhodes et al. 2013a, b). Our intestine
contains more microorganisms, especially bacteria, than all of our other colonized sites
combined. There are also populations of bacteria on the skin, in the urogenital tract,
mouth, nose, ears, and eyes.
In 2007, the National Institute of Health (NIH) launched the Human Microbiome
Project, also called Bthe second human genome project.^ This project included a number
of member organizations and repositories connecting to a central data repository known
as the Data Analysis and Coordination Center (DACC). The aim of this research
initiative was to characterize the role of microbiota in human health and disease.
Specifically, by utilizing emerging technologies in genetics, e.g., high-throughput
methods and DNA sequencing, to characterize the microbial communities that inhabit
the human body and explore the relationships between the microbiota and their human
hosts. This includes effects on human health and disease, development, physiology,
immunity, and nutrition (http://nihroadmap.nih.gov/hmp/). The potential benefit of this
research is highly promising and revolutionary (Hawkins and O’Doherty 2011; Robles-
Alonso and Guarner 2014): a better understanding of human nutritional requirements,
resulting in innovative food production and distribution strategies (Peterson et al. 2009);
infectious disease control and other public health benefits; increased knowledge of
effective microbiome-based intervention and successful manipulation; forensic tools
and application; personalized medicine and pharmaceutical improvements known as
Bpharmacomicrobiomics^ (Arumugam et al. 2011). Apart from large research initia-
tives, there has also been an increasing volume of translational research to explore how
the human microbiome can be modulated to improve health and avoid disease through
diets, probiotics, prebiotics, and microbial-based intervention.
In addition, given the impact of microorganisms on our health, there are also large-
scale efforts to chart our indoor and immediate outdoor microbiome environment.
Studies charting public restrooms, apartments, dust, hospitals, kitchens, and metropol-
itan subways were launched (Shamarina et al. 2017). The scientific findings of these
studies are useful for advancing strategies to protect populations and society, e.g., early
warnings for potential epidemics. Although these research projects may not directly
involve issues such as informed consent and results returning as biobanking human
microbiome do, as Shamarina et al. (2017) pointed out, such studies challenge our
perception of public health, safety, and privacy in the urban environment and may
inadvertently bring a negative image of microorganisms that would foster public fear of
such research. Although this kind of research is related to our theme, however, in this
paper, we limit our discussion on biobanking human microbiome samples which are
directly collected from individuals.

Human Microbiome Biobanks

Similar to biobanks storing human tissue samples, e.g., the UK Biobank and the
Icelandic Biobank, the types of specimens collected and the associated clinical
314 Asian Bioethics Review (2017) 9:311–324

information stored vary with the purpose and scope of the human microbiome biobank,
as well as the nature of the research.
Schwab et al. (2013) have identified at least three categories of research:

The first category is research in determining whether all human beings across
countries, race, and culture share a single identifiable Bcore^ microbiome. In
these studies, healthy individuals are recruited and normally their gut microbiota
derived from stool sample will be collected and analyzed; second research
category focus on how the microbiome is affected by individual genotypes and
environment, and whether changes in the microbiome cause, or predictive of
human disease. Research subjects in these studies are normally patients with a
specific condition; the third category of research may collect and store different
types of samples, including symbiotic microorganisms from different sites on or
within the human body. Some of these microorganisms have yet to be identified.

A few examples of large-scale studies may be illustrative. American Gut is an open-

source, community-driven effort to characterize the microbial diversity of the American
public and to understand how diet and lifestyle may contribute to health through each
person’s gut microbes. Disease-based biobanks like the cystic fibrosis biobank in
Toronto, Canada, have been established to facilitate sample and data sharing from
research into the link between disease progression and microbial dynamics in the lungs
of pediatric and adult patients. The Human Oral Microbiome Database (HOMD) is a
Web accessible resource for investigating oral microbe taxonomic and genomic infor-
mation which provides comprehensive information on the approximately 700 prokary-
ote species that are present in the human oral cavity (Chen et al. 2010). To examine
how the human microbiome evolves over time or in response to age, environment, diet,
lifestyle, medication, and disease, the Harvard Chan School awarded 4.9 million to set
up a collection that will create the world’s most comprehensive human microbiome
specimen collection, using samples from more than 25,000 individual participants over
a long time. Researchers aim to catalog the microbial populations across multiple body
sites from participants, combining that data with individual lifestyle, health, and genetic
information that has already been collected. However, such a prospective cohort study
will be challenging in terms of patient recruitment and retention, as well as sample
storage and data management.
Among various microbiome banks, Bstool banks^ in recent years have shown
considerable promise in treating patients with intestinal tract disorders, especially those
infected with Clostridium difficile (van Nood et al. 2013; Costello et al. 2016). This is
due to the increasing volume of clinical studies demonstrating that transplanting gut
microbial communities from healthy individuals to patients with a dysbiotic gut
microbiota could become a viable therapeutic option. This innovative therapeutic
option is called Fecal Microbiota Transplantation (FMT) (Borody and Campbell
2012; Borody and Khoruts 2011). Mid-2016, the US Food and Drug Administration
(FDA) waived the Investigational New Drug (IND) requirement for performing FMT,
but only for treatment of recurrent CDI that does not respond to standard therapies,
provided adequate informed consent from the patient is obtained (Food and Drug
Administration 2013). Although evaluation of the efficacy and safety of FMT is still
lacking, there is increasing enthusiasm from doctors, policymakers, and patients for
Asian Bioethics Review (2017) 9:311–324 315

expanding its applications (Ma et al. 2017a). Several companies have invested heavily
in the concept and at least 100 clinical trials are underway, 16 of them in China alone
(Amirtha 2016).
Biobanking the gut microbiome is a unique and much broader therapeutic approach;
it not only eliminates practical and psychological barriers in FMT but also contributes
to translational research in human gut microbiome research (Bolan et al. 2016). The US
FDA guidance defines a stool bank as an establishment that collects, prepares, and
stores FMT products for distribution to other medical institutions, healthcare providers,
or other entities for therapeutic or clinical research. Terveer et al. (2017) also suggest Ba
central stool bank should enable careful monitoring of treatment outcome, side effects,
and long-term effects of FMT.^ It should be noted that stool banks not only collect and
store gut microbes but also their genetic and metabolic profiles. In reality, most medical
professionals also welcome FMT bank. According to our recent questionnaire survey
on gastroenterologist clinicians, the majority of the respondents were greatly in favor of
the establishment of a fecal microbiota bank as it Bnot only shifts the burden of contact
with stools, but also avoids the privacy problems^ (Ma et al. 2017b).
Globally, stool banks have been established in some countries; the OpenBiome
project was launched in 2012 in Massachusetts, USA, and has provided stool for
13,000 FMT in USA and six other countries. Other research institutes and clinics are
following and have started banking healthy donors’ stool and patients’ own stool for
future medical or research use, for example, AdvancingBio in the USA, the Taymount
Clinic in the UK, the Netherlands Donor Faeces Bank (NDFB), Melbourne FMT in
Australia, Asian Microbiota Bank in Hong Kong, and the Chinese FMT Bank in China.
Most of these stool banks are non-profit. Knowledge gained from these banks, donors,
and patients will help to optimize and streamline the therapeutic use of stool samples.
Using high-throughput techniques will also make it feasible to identify and analyze all
the microorganisms associated with the human gut together with host genetics and to
understand how these contribute to changes in the gut microbial ecosystem.
With the increasing effort of human microbiome research, it is inevitable that a
growing number of biobanks will include a collection of microbiota specimens required
for genomic studies. In particular, gut microbiota biobanks and the associated genetic
information may become a valuable health resource. But, it also presents practical,
social, and ethical problems, some of which are distinct from those of biobanks that
store human tissue samples, including determining and selecting healthy donors,
managing and interpreting the unprecedented amount of biological data when the
relevance to disease is unknown, externalization and collaboration with other banks
and clinics (Bolan et al. 2016), and ethical issues like informed consent for both donor
and recipient, privacy, and results returning issues. The focus of this paper is to discuss
some of these ELSI questions in the context of human microbiome biobanks.
Informed by the scientific literature on human microbiome research and research
related to ELSI of biobanks, our discussion draws on our experiences in performing
FMT for more than 1500 people and establishing the Chinese FMT Bank (J. L. Ren),
familiarity with ethical issues in FMT and human microbiome research (Y. H. Ma), as
well as developing ethical guidelines for biobank research in China (R. P. Lei, H. Chen
and Y. H. Ma). We compiled a list of ethical concerns—all raised during our discus-
sions with clinicians, microbiologists, pharmacologists, informatics experts, bioethi-
cists, and biobank researchers. The ethical and social issues identified and discussed in
316 Asian Bioethics Review (2017) 9:311–324

this paper can be highly useful when developing guidelines or regulations for
microbiome research.

Nature and Characterization of Human Microbiome Samples

In this section, we focus on the ethical and social issues related to the nature and
classification of human microbiome samples, in particular, the fecal microbiota sample
and its regulation. The concept of a human microbiome has dramatic implications for
how we think of ourselves and the environment. As Gordon and colleagues explain,
human function is not simply determined by our own physiology, but includes the
microbiota that help regulate energy balance, digest food, and modulate the immune
system (Gordon et al. 2005). We are no longer individual organisms, but rather as
Rhodes et al. (2013a, b) assert Bsuperorganisms that include our own cells and a
fluctuating set of bacteria and viruses^ that share our body space and interact with
our own genome. From an evolutionary perspective, Bour coexistence with the
microbiome tells us that human evolution is not just human history^ (Rhodes 2016).
Nobel Laureate Lederberg (2006) believed the combined human-microbiome self is
more dynamic and more interactive than we are used to think of ourselves as being.
Moreover, the health of a human as a Bsuperorganism^ is determined by both Bintrinsic
properties such as human genetics, sex, diurnal cycles and age, and by extrinsic factors
such as lifestyle choices (food and drink, drug intake) and the acquisition of a stable
‘healthy’ gut microflora (the so-called microbiome)^ (Goodacre 2007).
With respect to stool banks, the classification of fecal microbiota samples is highly
relevant, as diverse understandings and definitions of fecal microbiota have a signifi-
cant impact on the social acceptability of FMT and how it is regulated (Ma et al.
2017a). The US FDA has regulated human feces as a biological product and drug based
on its effectiveness in cure, mitigation, and treatment of disease. This requirement aims
to ensure safety and therapy standardization of FMT. Under this regulation, doctors are
required to submit a time-consuming IND application before performing FMT for all
other diseases outside of treatment for CDI (e.g., inflammatory bowel disease, obesity).
This regulation has provoked anxiety and criticism among doctors and patients. Some
researchers have criticized this mandatory IND as Binappropriate^ and Bactually
harmful^ (Kelly et al. 2014), and lawyers commented that the drug paradigm of
regulating FMT fails to achieve its intended objectives (Sachs and Edelstein 2015).
Three areas of criticism have been identified: firstly, the challenge of product
characterization as fecal microbiota does not fit the definition of a drug. The Bprocessed
human stool used in FMT is a varied, complex mixture of microbes, metabolites and
human cells. It is almost impossible to identify the active ingredients, potency and
stability of this product, or to perfectly control the manufacturing process^ (Ma et al.
2017a). Therefore, the rigorous standards applied to conventional drugs are not appli-
cable to fecal microbiota. Second, regulating fecal microbiota as a drug may actually
dissuade doctors from using the product and limit access to care, especially for front-
line doctors who are not familiar with the IND application (Smith et al. 2014). Third,
researchers warn that the safety rules imposed by the FDA are Brestrictive^ and might
Bencourage people to seek treatment outside the medical establishment^ (Smith et al.
2014). In reality, patients have already advocated for at-home DIY FMT procedures
Asian Bioethics Review (2017) 9:311–324 317

and posted videos on social media. In contrast to the FDA classification of fecal
microbiota in FMT as a drug, many gastroenterologists consider it to be a Bvirtual
organ^ (Borody and Campbell 2012; Evans et al. 2013) and therefore FMT should be
regulated as Bhuman tissue.^ They also suggest FMT can be regulated under the same
safe standards used for transplanting blood, bone, skin, and egg cells. This regulation
could relieve the burden of the IND requirement for clinicians and enable wider access
to FMT.
However, apart from the practical considerations, characterizing fecal microbiota as
Bdrug,^ Bbiological product,^ Btissue,^ Borgan,^ or Bwaste^ may have important
philosophical and ethical implications. Philosophical concerns include should we
consider human microbiome as part of our self, or part of the environment? Are they
constitutive to our Bpersonal identity^? In this context, a strict dualistic dichotomy of
human versus non-human and self versus non-self that Hawkins and O’ Doherty (2011)
are concerned about inevitably collapses. On the other hand, from an ecological
perspective, human microbiome should be considered as part of human being due to
co-evolution and vital functions performed by microbiome. This belief underlies the
portrayal of the human gut microbiome as an Borgan^ inside of the human body.
Different categorization of fecal microbiota may also impact attitudes, beliefs, and
expectations about the risk and benefit of FMT (as well as other human microbiome-
derived therapies). For example, if fecal microbiota is regulated as Bdrug,^ this may
raise safety and risk concerns among patients and perhaps even doctors, particularly if
FMT is thought of as a Bnew drug^ that has not been widely tested. In contrast, if fecal
microbiota is regulated as Btissue,^ patients may regard FMT as merely a form of
transplantation, like blood transfusion, and thereby perceive it as more Bnatural^ and
Bless risk.^ This can lead some patients to overestimate their benefits and underestimate
the risks surrounding FMT. In addition, if fecal microbiota is regulated as Btissue^ and
FMT is perceived as comparable to blood transfusion, would it still be subject to
research ethics review? Although regulating FMT as Btissue^ rather than Bdrug^ may
relieve it of the burden of IND requirement and could enable wider access to FMT, the
risk of it being misused could increase and related issues may be overlooked.

Privacy

Privacy is a very important issue in ELSI discussions about biobanking because of the
sensitive nature of data (both clinical and genetic) stored, as well as the negative
consequences regarding privacy breaches. Recent studies in human microbiome re-
search have demonstrated that personal microbiomes contain enough distinguishing
features to identify an individual over time (Franzosa et al. 2015). Moreover, changes in
the microbiome could be indicative of past behavior. Travel to particular regions could
change a person’s microbiome by introducing new bacteria unique to a specific place.
Researchers have even observed that sexual habits can affect the microbiome of the
penis, making it possible to trace a man’s sexual behavior by obtaining a sample of his
genital microbiome (Ravel et al. 2011). In medicine, changes in gut microbiome have
been found associated with disease susceptibility, e.g., inflammatory bowel disease,
multiple sclerosis, and arthritis. It might also be possible to identify ethnicity, race,
socio-economic background, and nationality by analyzing sample of someone’s
318 Asian Bioethics Review (2017) 9:311–324

microbiome (Gupta et al. 2017). Meanwhile, there is still a lack of scientific consensus
on whether human microbiome data is uniquely identifying like human genetic data.
After all, human microbiome can be easily affected by changes in diet, lifestyle,
medication, time, and environmental factors. It is also highly possible that information
generated from an individual’s microbial profile at a specific time is not identifying at a
later point in time (Chuong et al. 2017).
However, the possibility of privacy breaches relating to microbiome data
cannot be ignored and warrants serious consideration. Firstly, when a human
microbiome profile is combined with human genetic and other types of informa-
tion, this could generate unprecedented personal-revealing information of a new
magnitude (Chuong et al. 2017), such as travel experience, sexual practice, and
consumption of alcohol and drugs. In addition, this information could be of
particular interest for people in forensic investigations or law enforcement and
could cause disastrous consequences to the person involved. This concern is
highly realistic, as actually, in many stool banks, the human gut microbiome
samples generally contain human cells and therefore the metagenomic data are
mixed with human DNA data. In a study interview with investigators, when asked
about attitudes towards this problem, some investigators were Bless assured by the
filtering process^ either because of Bcomputational limitations^ or because
Bportions of the human genome have yet to be mapped^ (McGuire et al. 2012), so
this mixture of DNA may be largely unavoidable (Schwab et al. 2013). Secondly,
without substantial further research, we want to advocate a precautionary approach
towards the validity of any conclusions regarding undisclosed identification of
individuals, or links to disorders. Similar to our concerns with direct-to-consumer
genetic testing, the interpretation of information may vary between labs and this
could result in premature or incorrect conclusions regarding susceptibility to
diseases. Furthermore, this also opens the door for some probiotic manufacturers
and companies to directly advertise their probiotic products to vulnerable populations
who could be misled into believing that they are Bat higher risk^ of certain
diseases based on their microbiome sample testing. Therefore, physicians and
scientists need to be cautious when handling this information to avoid labelling
some people as Brisky^ to some disease, especially in societies where there are
social stigma associated with mental illness and neurological disorders. Thirdly,
since human microbiome research may raise concern about possible social stigma,
discrimination, stereotyping, and abuse of information against certain groups,
protections should be provided for information arising from microbiome biobank.
It is important to examine whether existing regulations and protections are
adequate to protect people from discrimination based on their microbiome information
and whether modifications are needed. Some researchers in Western countries
have already suggested that the Genetic Information Nondiscrimination Act
(GINA) and Health Insurance Portability and Accountability Act (HIPAA) in the
USA and Personal Information Protection and Electronic Documents Act
(PIPEDA) in Canada should be amended and extended to apply to human microbial
samples (Hawkins and O’Doherty 2011; Gligorov et al. 2013). We agree with
their proposals, since the genetic data of microbiome we carry may be considered
to be almost as personal as our own genome. It therefore seems reasonable to
regulate both technologies at the same level in order to safeguard against undue
Asian Bioethics Review (2017) 9:311–324 319

privacy violation. However, in many developing countries, this area of research

remains unregulated and there is a clear need to establish regulatory processes that
address the unique challenges of human microbiome research in different contexts.
Yet, we should also bear in mind that possible psychological and social harms to
individuals should not be exaggerated and allow fear, panic, superstition, and
stigmatization of sensitive populations spread among the public, rather than scientific
evidence. We need to engage and protect people in research rather than warn them by
premature findings. Schwab et al. (2013) have proposed a Bcommunity consultation^
approach to participatory research which may be useful for professionals who are
engaged in microbiome research involving various specific populations.

Informed Consent

Obtaining informed consent from research participants is a well-established moral

and legal obligation. In human tissue biobanking, discussions of consent concen-
trate on how to ensure valid consent when the nature of the research as well as the
potential risks and benefits of participation are unknown, and when we are unable
to predict future research and the potential risks associated with it. For human
microbiome biobanking, personal data is typically collected and linked to banked
microbiota samples. It is also common practice to store these samples and asso-
ciated genetic information (both host and microbiota) for future research use.
Given our limited knowledge about the human microbiome, these concerns are
equally challenging in microbiome biobanking as it is impossible for biobank staff
to provide an explanation about specific research using microbiome samples.
Currently, participants may simply be asked to accept the uncertainty inherent to
conducting microbial research as a condition of participation (McGuire et al.
2008), but this practice raises similar questions as in human biobank regarding
the erosion of research subjects’ protection of an individual’s autonomy in
decision-making (Caulfield et al. 2003). A number of proposed solutions and
consent modes have been suggested to this issue, including broad consent, tiered
consent, dynamic consent, re-consent procedures, and centralized governance
mechanisms (Greely 2007; Caulfield and Murdoch 2017; Budin-Ljosne 2017;
Mello and Wolf 2010). The choice of consent mode is based on the nature and
benefit/risk ratio of the biobank research. However, a unique problem in human
microbiome research relates to the stability and dynamic nature of microbiome
samples over time. It is possible that a microbiome sample collected in childhood
may not be identifiable to the same person over the long term, or an individual’s
microbiome sample cannot be tracked back to the donor when he or she takes
antibiotics. This fact raises the issue of the value and necessity of re-consent in
human microbiome biobanking as it may be both unnecessary and unfeasible.
Given this, the severity of the privacy concerns is also difficult to determine or
compare with human genetic information, as the issue of identifiability is compli-
cated and dynamic.
Reflecting on popular accounts of research ethics history, Rhodes (2016) has argued
that the tradition of research ethics regulation gives primacy to autonomy and informed
consent of human subjects because it were designed for clinical trials which may
320 Asian Bioethics Review (2017) 9:311–324

expose a group of subjects to possibly serious harm. In contrast, biobank research and
studies to advance personalized medicine will require broad participation to provide
samples while often exposing participants to only Bde minimis^ risks of physical harm
(Rhodes et al. 2013a, b). She strongly calls for adjustment in our regulations to
reasonably accommodate the differences between clinical trials and biobank research
and also advocates for the obligations of participants to do their fair share in advancing
biomedical science.
The character of groups involved in microbiome biobank research also needs
serious consideration on their capacity, voluntariness, and vulnerability. For ex-
ample, questions arise when children become research subjects at an age when
they are unable to give informed consent. Some microbial studies will collect
infant and children stool samples (De Filippo et al. 2017) and parental consent for
minors in these studies adds new challenges. Moreover, concerns regarding the
vulnerability of research participants in fecal microbiota transplantation are par-
ticularly notable. For example, as Ma et al. (2017a) point out, the autonomy of
IBD patients as a FMT target population may be Bcompromised by their stress and
desperation, affecting their ability to give informed consent.^ Their capacity to be
informed may also be affected by a diminished ability to appropriately process
information about risk. On the other hand, a study shows that recruitment of fecal
donors for FMT banks can also present challenges, as only a small percentage
(2%) of those enrolling ultimately serve as donors (Paramsothy et al. 2015). It also
raises the question of compensating donors, should volunteers be rewarded finan-
cially for giving stool samples to incentivize stool donation? How can we deter-
mine Bsuitable healthy donor^ and Bhealthy microbiota^? These concerns are
potentially more challenging in this context than for tissue banking.
There are also concerns about the effectiveness of informed consent documents used
in some human microbiome research as they were too long and complex. What
(minimum) information should be included in informed consent? Biobanking human
microbiome also needs to take into account the cultural acceptability and individual
psychological factors. For example, the procedure of collecting vaginal microbiome
may be against some religious belief, and donating or accepting the fecal transplant
may cause disgust and the Byuck^ reaction.

Return of Results to Participants

The issue of returning results has been a key challenge in human subjects’ research, as
the question of whether and to what extent research participants should be informed
about research results is currently controversial (Ravitsky and Wilfond 2006). In human
microbiome research, this issue becomes more complicated as the validity, reliability,
relevance, and clinical significance of the data is largely uncertain. Returning aggre-
gated research results to all subjects may be considered an ethical imperative, while
debates are focused on return of results specific to individuals and whether participants
should receive their individual data.
The return of results to individuals is an important matter as these results may
potentially benefit individuals. In the context of human microbiome biobanking,
researchers may discover that a research participant has an increased risk of
Asian Bioethics Review (2017) 9:311–324 321

obesity or colorectal cancer as recent studies have shown a correlation between

the gut microbiota profile and these diseases (He and Shi 2017; Omer and Atassi
2017; Chen et al. 2017). Returning these findings to participants would allow
them to change lifestyle, diet, behavior, or even take probiotics or prebiotics that
might reduce the risk of obesity or colorectal cancer. However, scholars are also
concerned that Bthe current state of knowledge of the human microbiome is too
premature to make any conclusions at this time regarding disease risk and
susceptibility or how the microbiome may be altered to restore health^
(McGuire et al. 2008). In interviews with investigators (McGuire et al. 2012)
involved in the Human Microbiome Project (HMP) in the USA, researchers
reported that investigators raised three main barriers to returning individual-
level results to participants. The biggest barrier is simply that researchers do
not know what the data mean in terms of health and disease, as human
microbiome research is still in its infancy. Some raised the fact that data is not
that meaningful to an individual, but is more meaningful on a population level.
Others raised the recent findings that individuals could be colonized with various
bacteria or pathogens, but that the colonization may be difficult to distinguish
from infection at mucosal surfaces. The second identified barrier pertains to
communicating results to subjects in a way they can understand. An investigator
stated Bfigure out what level of detail and how to present it so that it’s maximally
informative without just sort of deluging people with a lot of information.^ The
third barrier identified by investigators was related to the HMP results’ lack of
clinical validation. Again, because human microbiome research was so new and
most results were preliminary and not reproduced, investigators felt that
returning results would be inappropriate.
Wolf et al. (2012) recommend that researchers have an obligation to report findings
that are analytically valid, reveal an established and substantial risk of a serious health
condition, and are clinically actionable, and should be returned to participants and
perhaps public health authorities. For example, if an individual is tested HIV positive,
or positive in other sexually transmitted disease, he or she should be informed of the
test result and counselling should be provided. However, we argue that this testing
should be included in the informed consent process; individuals who do not want to
know their test results can choose not to participate.
With the growing knowledge about the human microbiome, informing an individual
about his or her microbiome profile may provide more possibilities and opportunities
for early diagnosis, treatment, and risk management. In addition, unlike the human
genome which remains relatively static throughout life, the human microbiome is
dynamic and subject to intervention, which is or at least will be more clinically
actionable than human genetic data (Chuong et al. 2017). For example, Zakutar et al.
(2014) found that analysis of gut microbiota could potentially be used as a screening
tool for early detection of colorectal cancer. Another study suggests gut microbiota
shape the response to cancer immunotherapy and a planned trial will manipulate
patients’ microbiome to help this response (Kaiser 2017). Consequently, the ratio
between benefits of early clinical intervention and the psychological or social harm
to individuals may need to be reconsidered. The possibility of results return should be
addressed in the consent process in a transparent and understandable manner to avoid
fear and therapeutic misconception.
322 Asian Bioethics Review (2017) 9:311–324

Conclusions

It is important to consider the social and ethical issues early on in human microbiome
biobank research to be proactive and prepared in facing challenges. In this paper, we
have briefly explained the concept of the human microbiome biobank and then focused
on the debates over the nature and characterization of human microbiome sample and
how different understandings have an impact on benefit/risk evaluation, privacy,
informed consent, and return of results. We agree that based on the possibility to re-
identify individual donors, human microbiome samples should be treated with the same
privacy safeguards as human tissue samples. We have examined various understand-
ings and definitions of fecal microbiota that have a significant impact on its applications
in medical settings, e.g., the social acceptability of FMT. We also propose returning
individual results should be addressed in the consent process to respect participants and
avoid fear and therapeutic misconception. We suggest that regulation of stool banking
and other types of human microbiome biobanking is urgently needed with respect of
informed consent, privacy protection, return of results, and particularly, safekeeping
data derived from human microbiome.
As human microbiome research advances, more research initiative may require the
participation of diverse and broad population across race, culture, and society while
often exposing participants to very small risks. These changes may require a re-
evaluation of the benefits and harms ratio and design of new consent and governance
mechanism to better accommodate changes. We believe engaging with these challenges
can foster a meaningful and collaborative endeavor to better formulate policy guide-
lines for human microbiome research and its applications.

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