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Key Points The microbiome has been implicated in the development of obesity. Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications. Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an “endocrine” organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.
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published: 19 February 2016
doi: 10.3389/fcimb.2016.00015
Frontiers in Cellular and Infection Microbiology | 1February 2016 | Volume 6 | Article 15
Edited by:
Daniel Hassett,
University of Cincinnati, College of
Medicine, USA
Reviewed by:
Marina Santic’,
University of Rijeka, Croatia
V. K. Viswanathan,
The University of Arizona, USA
Lily Q. Dong,
University of Texas Health Science
Center at San Antonio, USA
Wayne S. Cutfield;
Justin M. O’Sullivan
Received: 22 October 2015
Accepted: 25 January 2016
Published: 19 February 2016
Jayasinghe TN, Chiavaroli V,
Holland DJ, Cutfield WS and
O’Sullivan JM (2016) The New Era of
Treatment for Obesity and Metabolic
Disorders: Evidence and Expectations
for Gut Microbiome Transplantation.
Front. Cell. Infect. Microbiol. 6:15.
doi: 10.3389/fcimb.2016.00015
The New Era of Treatment for
Obesity and Metabolic Disorders:
Evidence and Expectations for Gut
Microbiome Transplantation
Thilini N. Jayasinghe 1, Valentina Chiavaroli1, David J. Holland2, Wayne S. Cutfield1, 3*and
Justin M. O’Sullivan 1, 3*
1Liggins Institute, The University of Auckland, Auckland, New Zealand, 2Department of Infectious Diseases, Counties
Manukau Health, Auckland, New Zealand, 3Gravida: National Centre for Growth and Development, Auckland, New Zealand
Key Points
The microbiome has been implicated in the development of obesity.
• Conventional therapeutic methods have limited effectiveness for the treatment of
obesity and prevention of related complications.
Gut microbiome transplantation may represent an alternative and effective therapy for
the treatment of obesity.
Obesity has reached epidemic proportions. Despite a better understanding of the
underlying pathophysiology and growing treatment options, a significant proportion of
obese patients do not respond to treatment. Recently, microbes residing in the human
gastrointestinal tract have been found to act as an “endocrine” organ, whose composition
and functionality may contribute to the development of obesity. Therefore, fecal/gut
microbiome transplantation (GMT), which involves the transfer of feces from a healthy
donor to a recipient, is increasingly drawing attention as a potential treatment for obesity.
Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary.
Here, we summarize benefits, procedures, and issues associated with GMT, with a
special focus on obesity.
Keywords: gut microbiome transplantation, microbiome, microbiota, obesity, treatment
Obesity has recently been identified as a disease by the American Medical Association with >33% of
the world’s adult population (20 years and older) overweight or obese (World Health Organization,
2014). Sadly, this is projected to increase to the point where up to 57.8% of the world’s population
aged 20 and over is either overweight or obese (World Health Organization, 2014). There are
various causative factors that contribute to the development of obesity including genetics (Wang
et al., 2011a), low levels of physical activity and exercise, poor diet and other unhealthy behaviors.
Obesity is a major risk factor for diabetes, hypertension, and metabolic syndrome. Despite the
promotion of numerous strategies for the prevention and treatment of obesity, most patients are
refractory to treatment. Thus, new approaches are currently being sought to reduce the financial,
social, and health consequences of the obesity epidemic.
Jayasinghe et al. Gut Microbiome Transfer
The human gut contains an extensive population of microbes
(the gut microbiome) that effectively constitute a microbial
“endocrine organ” (Cani and Delzenne, 2007; Clarke et al.,
2014). Recent research has implicated these microbes as having
a significant role in the development of obesity (Bäckhed et al.,
2004; Ley et al., 2005, 2006b; Turnbaugh et al., 2006, 2009;
Backhed et al., 2007; Zhang et al., 2009), diabetes (Larsen et al.,
2010; Qin et al., 2012), and cardiovascular disease (Ordovas and
Mooser, 2006; Wang et al., 2011b; Howitt and Garrett, 2012;
Tang and Hazen, 2014). Therefore, environmental effects on these
microbes and our ability to manipulate them in a controlled
manner are under increasing scrutiny.
Fecal/gut microbiome transplantation (GMT; Box 1) has
been suggested as a new method of altering the gut microbiota
that may lead to beneficial metabolic changes (Smits et al.,
2013). Modifications of the host’s microflora by GMT were first
performed in the 1950s to treat pseudomembranous colitis now
known to be due to Clostridium difficile infection (CDI) (Eiseman
et al., 1958). Since then, GMT has been successfully used for CDI
treatment and is increasingly considered the treatment of choice
for chronic pseudomembranous colitis (Gough et al., 2011).
Despite the fact that GMT has been shown to improve insulin
sensitivity in adults with features of metabolic syndrome (Vrieze
et al., 2012), its application as a therapy for other conditions,
including obesity, is still experimental. As such, it is still unclear
how, when, or under which circumstances GMT should be
performed. Here, we will address the procedures, benefits, and
issues associated with GMT, with a special focus on obesity.
A human being is more than the sum of their “own
cells.” Rather, the 10 trillion human cells that we each
contain constitute <10% of the cells within our bodies with
the remaining 100 trillion cells, that reside in and on the
human body, being of microbial origin (Ley et al., 2006a). As
a consequence of this, our 20,000 human genes (Yang et al.,
2009) are vastly outnumbered by the human microbiome’s 2
to 20 million microbial genes (at least 100 times the number
of human genes; Knight, 1993). These microbial genes (99%)
are mostly encoded by the bacteria within the human gut (Qin
et al., 2010). It is now becoming increasingly clear that these
microbial communities interact with the human host at many
levels, which include the local and systemic gut and immune
function (Macpherson and Harris, 2004).
The microbes comprising the human microbiome generally
have a symbiotic relationship with the host. The human intestine
provides them with a supply of nutrition and a relatively stable
Through-out this manuscript we refer to gut microbiome transplantation (GMT) and not fecal microbiome transplantation (FMT). Predominant amongst our reasons for
this minor change in terminology is the public attitude and perception of products and treatments derived from feces as being “dirty” or “unhygienic” (Brandt, 2012;
Leslie et al., 2014). These prejudices are ingrained and continually reinforced by the testing and notifications of fecal contamination of public drinking and bathing
sources that form part of a public system to identify and prevent disease outbreaks. Moreover, the eating of feces (i.e., coprophagia) is recognized as a symptom of
mental health disorders (Zeitlin and Polivy, 1995). Collectively, these conscious and sub-conscious prejudices combine to reduce the potential acceptability of fecal
transfers. Therefore, in order for microbiome transfer to be implemented as a widespread treatment for chronic and non-acute disorders, it must be promoted in a way
that minimizes the fecal stigma. We propose that the first step in this journey is the use of the term GMT.
living environment. In return, microbes play a vital role in our
body by synthesizing metabolites (e.g., vitamin K, thiamine,
biotin, folic acid, vitamin B12;Gorbach, 1996), digesting non-
starch polysaccharides into additional nutrients for the human
host (Vercellotti et al., 1977), providing a physical barrier in the
form of a biofilm to boost the immune system, and protecting
from pathogens (Mazmanian et al., 2005). Moreover, intestinal
microbes may be also an important factor for brain development
(Diaz Heijtz et al., 2011), metabolic function, and hormones and
neurochemicals production (Lyte, 2013).
The human gut is generally considered to be sterile in utero (Ley
et al., 2006a; Maynard et al., 2012), with microbial colonization
beginning during delivery when newborns come into contact
with maternal womb, vaginal, fecal, and skin microbes (Lee and
Polin, 2003). However, meconium of healthy neonates, collected
within 2 h of delivery from healthy mothers, has been shown
to contain microbes (e.g., E. fecalis,S. epidermidis, and E. coli;
Jiménez et al., 2008). This has led to the promotion of hypotheses
that bacteria from the maternal gut are transferred to amniotic
fluid, possibly via the circulation (Kornman and Loesche, 1980),
and through swallowing of amniotic fluid into the fetal gut
(Goldenberg et al., 2008; Neu and Rushing, 2011). Given that
a fetus swallows 400–500 ml of amniotic fluid per day late in
gestation (Goldenberg et al., 2008; Neu and Rushing, 2011), only
low numbers of microbes would be required within the amniotic
fluid to facilitate microbial colonization of the fetal gut. This
mechanism of fetal colonization is supported by the detection of
microbes and microbial products within amniotic fluid isolated
from healthy mothers (Li et al., 2014). Finally, microbes have
been isolated from the umbilical cord (Jiménez et al., 2005)
and placenta (Aagaard et al., 2014) of healthy infants (without
infection or inflammation). Collectively these observations are
consistent with the hypothesis that fetus is colonized by microbes
before birth.
Mode of delivery (e.g., vaginal delivery or cesarean section)
has been observed to have a significant impact on the microbiota
within the newborn gut (Dominguez-Bello et al., 2010; Neu and
Rushing, 2011). Interestingly, children born by cesarean section
have a greater risk of obesity in later childhood, suggesting
a causal link between early gut bacterial colonization and
later obesity (Blustein and Liu, 2015). Cesarean section has
been associated with a greater likelihood of C. difficile and
lower number of Bacteroides spp. colonization (Penders et al.,
Frontiers in Cellular and Infection Microbiology | 2February 2016 | Volume 6 | Article 15
Jayasinghe et al. Gut Microbiome Transfer
2005, 2006). Gestational age of newborns (e.g., were they born
prematurely, at term or post-term) also correlates with gut
microflora composition. The gut of preterm infants contains
higher levels of C. difficile compared to full term infants (Penders
et al., 2006). Moreover, data obtained from short-term stool
culture have shown that colonization by Bifidobacterium and
Lactobacillus is delayed in preterm infants, whereas colonization
by potentially pathogenic bacteria (especially E. coli) is increased
(Westerbeek et al., 2006; Butel et al., 2007).
During infancy, diet is one of the many contributors to
the development of gut microbiome (Koenig et al., 2011). The
importance of diet is reinforced by observations that breast-
fed infants have more Bifidobacteria than formula-fed infants
(Koenig et al., 2011). By contrast, formula-fed infants have a
lower microbial density, yet higher diversity of other microbial
species compared to breast-fed infants (Harmsen et al., 2000;
Koenig et al., 2011). After the introduction of solid food into
the diet, at weaning, an adult-like microbial ecology begins to
develop within the gut (Fanaro et al., 2007).
By 3–4 years of age, the gut microbiome composition is
dominated by two phyla (>90% of bacteria): Firmicutes, which
are pro-inflammatory and obesogenic, and Bacteroidetes, which
protect from these effects (Cani and Delzenne, 2007; Clarke
et al., 2014). Once established, the gut microbiota remains
relatively stable throughout the life of healthy adults albeit
subject to temporary modifications (Palmer et al., 2007). There
are two broad groups of influences on the gut microbiome:
dynamic factors (diet and drugs) and less dynamic factors
(genetic, early events/exposures, and lifestyle factors). Diet
contributes to dynamic changes in gut microbiome and
influences approximately half of the microbial population activity
(Zhang et al., 2010). Conversely, other factors tend to maintain
the activity of the microbial population. However, microbial
composition undergoes changes in the elderly (Tiihonen et al.,
2010), which include increases in the levels of Lactobacilli,
Coliforms, Clostridium, and Enterococci and a decrease in the
number of Bifidobacterium (Mitsuoka, 1990). The presence of
imbalance in the composition of the gut microbiota at all ages,
which is also known as “dysbiosis,” is associated with obesity
development (Bäckhed et al., 2004; Ley et al., 2005; Turnbaugh
et al., 2009).
In otherwise healthy individuals, diet quality is the major
modulator of the gut microbiota, accounting for 57% of host
gut bacterial variation (Zhang et al., 2010). Diet-induced changes
to gut microbial content are relatively rapid, occurring over 3–4
days and are readily reversible (Walker et al., 2011). Modification
of gut microbiome can also be achieved by use of prebiotics
and probiotics, and antibiotics (Walker et al., 2011; Binns, 2013;
Modi et al., 2014). Prebiotics and probiotics appear to support a
more favorable gut environment (Binns, 2013). However, these
supplements need to be consumed regularly to maintain changes
in gut microbiota (Binns, 2013), as it is unclear how long these
changes last in the gut. Short- and long-term modifications
of gut microbiome can also result from antibiotics, which
reduce diversity by promoting the elimination of some bacterial
species and antibiotic resistance by horizontal transfer within
the remaining flora (Modi et al., 2014). Alcohol consumption
also affects composition of gut microflora (Mutlu et al., 2012),
with chronic alcohol consumption causing microbial dysbiosis, a
reduction in the number of Bacteroidetes and an increase in the
numbers of Proteobacteria present in the gut (Mutlu et al., 2012).
Alterations in gut microbiome in alcoholic subjects correlate with
increased levels of serum pro-inflammatory toxins (Mutlu et al.,
2012). However, a recent study on microbiome development
showed that microbial metabolites and their metabolic pathways
are constant from birth, although microbial diversity increases
with age and becomes more consistent from the age of 3 years
(Kostic et al., 2015).
Each individual has their own unique microbial population
whose composition is affected by host genetic make-up, history of
exposure to microbes, age, diet, environment, and geographical
location (The Human Microbiome Project Consortium, 2012;
Ursell et al., 2012; Yatsunenko et al., 2012). Moreover, even within
an individual there are a myriad of distinct environments each
of which is colonized by different microorganisms (e.g., skin,
oral cavity, gastrointestinal, respiratory, and urogenital tracts;
Gerritsen et al., 2011). It is universally accepted that the high
surface area and availability of nutrients make the gut an ideal
site for microbial growth (Gebbers and Laissue, 1989; Sekirov
et al., 2010). However, the gut microbiota composition changes
at different sites within the gut (Zoetendal et al., 2002) and even
within the different layers of the gut epithelium (Swidsinski et al.,
2005). Despite this complexity, the ease of collection and the high
microbial content (Hütter et al., 2012) mean that fecal matter
is generally used to study “the gut microbiome.” Therefore,
despite the fact that the numbers of bacteria are several orders
of magnitude larger in the distal colon, which seems to have
a relatively uniform composition of microbes (Whitman et al.,
1998; Eckburg et al., 2005; Ley et al., 2006a; Gerritsen et al.,
2011), this does not reflect the situation throughout the entire
gut. As such, it must be borne in mind that fecal bacteria do not
necessarily inform on the composition of the microbiome within
the distinct environments that are present throughout the gut and
are characterized by differing levels of pH, oxygen levels, and food
transit rates.
The application of metagenomic techniques (Kim et al., 2013)
to the study of the composition, functional capacity, ecology,
and integration of human microbiota with human cellular
metabolism (Tremaroli and Bäckhed, 2012) is increasing our
knowledge of how this “microbial organ” integrates into the
human system. Metagenomic techniques overcome limitations
of conventional bacterial cell culture and other molecular
techniques that have been applied to the study of the
gut microbiome (Table 1;Aslam et al., 2010). The Human
Microbiome Consortium, the European Consortium of the Meta-
HIT and the International Human Microbiome Consortium
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Jayasinghe et al. Gut Microbiome Transfer
TABLE 1 | Techniques used for the analysis of microbial communities.
Category Advantages Disadvantages
Denaturing gradient gel electrophoresis (DGGE) A comparative tool for the study of inter-sample
microbial composition. Useful for studying microbial
population changes over a specific time period (Vaughan
et al., 2000).
Specific taxonomic information can be obtained by band
extraction followed by re-amplification and sequencing
(Heuer et al., 1999; Riemann and Winding, 2001).
Less expensive than other techniques.
• Bias due to PCR (von Wintzingerode et al., 1997)
and different DNA extraction rates (Theron and
Cloete, 2000). Provides a semi-quantitative measure
of species abundance (Vaughan et al., 2000).
Limited by cultivation techniques, especially for strict
anaerobes (Vaughan et al., 2000).
The ecological role of microbes cannot be determined
(Heuer et al., 1999).
16S amplicon sequencing Culture independent technique (Rajili ´
c-Stojanovi ´
c et al.,
2007) used to detect a wide range of microbes by
amplification and sequencing of variable regions within
the16S rRNA sequence (Vaughan et al., 2000).
PCR bias (Sipos et al., 2010; Schloss et al., 2011).
• On its own, it does not inform on microbes
functionality within samples (Vaughan et al., 2000).
Metagenomics, metatranscriptomics, and
Culture independent techniques that identify gene
composition and functional outputs of the microbes
present in a sample (Verberkmoes et al., 2009).
Ideally performed as a combination of metagenomics
(populations’ DNA complement), metatranscriptomics
(population’s RNA composition), and metaproteomics
(population’s protein composition) (Verberkmoes et al.,
Expensive (Wooley and Ye, 2009).
Complex bioinformatics (Meyer et al., 2008).
Extraction biases.
are currently developing and applying these techniques to
understand microbial effects on human health and diseases (Kim
et al., 2013).
Conventional techniques for the identification and
characterization of microbial communities are mostly
culture dependent and are unable to easily identify all of
the microorganisms present and functional contributions
that specific microorganisms make to the complex biological
environments in which they exist (Verberkmoes et al., 2009).
Despite their expense, metagenomic studies overcome many of
these limitations.
Four bacterial phyla (i.e., Firmicutes,Bacteroidetes,
Proteobacteria, and Actionobacteria) account for the majority of
the bacteria present in the human gut (Khanna and Tosh, 2014).
Typically 60% of the bacteria present in the human gut belong
to the gram positive Bacteroidetes or gram negative Firmicutes
phyla (Bäckhed et al., 2005). The most commonly found gut
bacteria genera in adults are Bifidobacterium,Lactobacillus,
Bacteroides,Clostridium,Escherichia,Streptococcus, and
Ruminococcus (Conlon and Bird, 2015). Individually and
collectively, these bacteria produce a vast range of microbial
products that include enzymes for carbohydrate metabolism (Xu
et al., 2003), short chain fatty acids (SCFA) (Bergman, 1990),
lipopolysaccharide (LPS) (Munford, 2008), and secondary bile
acids (Nicholson et al., 2012). These microbial products can enter
into the human circulation where they contribute to energy flux
in the human, or cause inflammation and other complications
(Tehrani et al., 2012; Trompette et al., 2014).
The gut microbial composition is distinctive in obese
individuals, and tends to show reduced complexity (Turnbaugh
et al., 2009). For example, obese mice have reduced numbers
of Bacteroidetes and increased numbers of Firmicutes when
compared to lean mice (Ley et al., 2005). These changes in
gut microbial populations have significant implications for
energy homeostasis, as a 20% increase in Firmicutes and a
corresponding 20% decrease in Bacteroidetes is estimated to
provide an additional 150 kcal of energy per day to an adult
human (Jumpertz et al., 2011). Lactobacillus numbers have also
been observed to increase in obese people, while anorexic patients
show higher numbers of Methanobrevibacter smithii (Armougom
et al., 2009).
Early research into the relationship between the gut
microbiome and obesity has used 16S ribosomal RNA (rRNA)
gene sequences to examine microbial diversity in obese and
lean individuals. Numerous studies have found phylum-wide
differences in lean or obese individuals (Eckburg et al., 2005; Ley
et al., 2006b; Frank et al., 2007). However, findings on the relative
proportions of the main phyla in obese and lean individuals
are contradictory (Duncan et al., 2008; Turnbaugh et al., 2009;
Schwiertz et al., 2010; Bervoets et al., 2013; Colson et al., 2013;
Ferrer et al., 2013). Meta-analysis has shown that the microbial
changes associated with obesity are not simply phylum based but
are the result of a collection of numerous small differences within
the overall population structure (Walters et al., 2014). Therefore,
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Jayasinghe et al. Gut Microbiome Transfer
it is important to look at the overall composition of the gut
microbial population structure as an indicator of obesity rather
than simply the proportion of Bacteroidetes to Firmicutes.
Type 2 diabetes has also been linked with gut microbiota that
differ from that found in a healthy individual (Larsen et al., 2010;
Qin et al., 2012). Patients with type 2 diabetes have reduced
level of butyrate-producing bacteria and more pathogenic
bacteria (Qin et al., 2012). These patients also show more
Betaproteobacteria and reduced Firmicutes and Clostridia levels
compared to healthy subjects (Larsen et al., 2010). Furthermore,
a correlation has been observed between Bacteroidetes to
Firmicutes ratio and plasma glucose concentration in type 2
diabetic and obese patients (Larsen et al., 2010; Schwiertz et al.,
2010). With these observations, it is clear that manipulating the
microbiome composition may represent a novel approach for
preventing and treating obesity and related alterations.
Several recent in-depth reviews provide detailed information
about potential mechanisms through which the microbiome is
linked to the development of obesity (Hartstra et al., 2014;
Gérard, 2015). The association between characterization of an
altered gut microbiome in obese or diabetic subjects does not
demonstrate cause and effect. However, there are indications
that the gut microbiome actively contributes to the development
of obesity. Specifically, Backhed et al. compared the fat mass
of germ-free and conventionally raised mice, and showed that
intestinal microbes are able to control fat storage (Bäckhed et al.,
2004). Similarly, Turnbaugh et al. introduced an “obesogenic
microbiota” to germ-free mice and found that mice with
obesogenic microbes developed more body fat than those with
“lean microbiota” (Turnbaugh et al., 2006).
Various mechanisms have been proffered to explain the
association of an “obese microbiota” with higher fat content in
mice (Bäckhed et al., 2004; Ley et al., 2005; Turnbaugh et al.,
2006; Hartstra et al., 2014). Most simply, microbial mediated
degradation of dietary fiber to SCFA contributes additional
calories to the host (Bäckhed et al., 2004; Hartstra et al., 2014).
In addition, SCFAs, notably butyrate, facilitates enhanced insulin
sensitivity and fatty acid oxidation in muscle and reduced hepatic
lipogenesis as well as increased satiety (Hartstra et al., 2014).
The way in which butyrate leads to these changes is unclear,
however it is likely to involve the activation of the G protein
coupled receptors GPR41 and GPR43, which are involved in
glucose metabolism (Hartstra et al., 2014). Moreover, SCFA and
bacterial lipopolysaccharides activate Toll-Like receptor 4 (TLR4)
and signal intracellular inflammatory pathways related to the
induction of insulin resistance and increased adiposity (Tsukumo
et al., 2007; Tehrani et al., 2012).
Turnbaugh et al. observed a higher content of SCFAs (e.g.,
butyrate and acetate) in the large intestine of obese mice
(Turnbaugh et al., 2006) consistent with a mechanism that
involves increased absorption of SCFA (Bäckhed et al., 2004).
In addition, comparisons of normal mice on a high-fat diet
with germ free mice on the same diet have demonstrated that
the gut microbes can reduce the expression of host fasting-
induced adipose factor/angiopoietin-like protein-4, a lipoprotein
lipase inhibitor (Ley et al., 2005). Reduced expression of fasting-
induced adipose factor increases lipoprotein lipase activity and
triglycerides storage in hepatic cells (Bäckhed et al., 2004), again
contributing to alterations to patterns and levels of fat deposits.
Despite these potential mechanisms, the exact contribution(s)
that changes in the proportions of Firmicutes to Bacteroides
species make to the development of obesity remains unknown
(Ley et al., 2006b). More work is required to more accurately
understand the contributions of the many proposed mechanisms
linking the gut microbiome with obesity, particularly in humans.
Lifestyle modifications are an important part of obesity
management. However, lifestyle interventions (such as diet and
exercise) have not consistently led to appreciable weight loss
(Golan et al., 1998). Furthermore, pharmacotherapy may have
negative impacts on the physiology and psychology of obese
patients (Collins, 1988; Hill et al., 1994; Hill, 2007). Surgical
interventions (e.g., Bariatric surgery) can be effective for short
term-to-medium-term weight management in severely obese
patients (Gloy et al., 2013). However, there are significant
risks associated with surgical interventions [e.g., dumping
syndrome (rapid gastric empting), micronutrient malabsorption,
cholelithiasis, and hypoglycaemia] (Puzziferri et al., 2014; Tack
and Deloose, 2014) and the treatment is expensive (Encinosa
et al., 2005). Therefore, new approaches for the prevention and
treatment of obesity are required. GMT represents an excellent
and economic (Encinosa et al., 2005) option for individuals who
are unable to lose weight by lifestyle measures, or those who
cannot undergo surgical treatment.
As gut microbes have been implicated in the development
of obesity (Turnbaugh et al., 2006), replacement of a microbial
population (“bad” microbes) that promotes obesity with a
population that promotes a healthy state (“good” microbes) may
represent a possible treatment. The question remains: how do
you change the entire flora of an individual at once? GMT with
fecal bacteria transferred from unaffected individuals to affected
recipients has been suggested as a promising method of altering
and improving gastrointestinal microbiota and human health
(Aroniadis and Brandt, 2013; Smits et al., 2013).
GMT uses live microorganisms as a potential intervention
that “confers a beneficial health effect on the host.” Thus, the
fecal samples can be considered a probiotic (Park and Bae,
2015). However, unlike typical probiotics, GMT doesn’t modify
the recipient’s gut flora using microorganisms associated with
fermentation. Instead, GMT modifies the recipient’s gut flora
using a community of organisms that was isolated from a healthy
gut—that is the same biological niche. This approach is essential
for the modification of the gut flora in obesity because of the
multiplicity of small, yet predictive, differences between the flora
of obese and lean individuals (Walters et al., 2014).
GMT is not new. In the fourth century A.D., Chinese patients
suffering from severe diarrhea were given oral fecal suspensions
(Zhang et al., 2012). Likewise, in the sixteenth century stool was
used to treat diarrhea, fever, vomiting and constipation (Zhang
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Jayasinghe et al. Gut Microbiome Transfer
TABLE 2 | Mice studies on gut microbiome transplantation.
Mouse model Treatment Outcome References
Adult germ-free
C57BL/6 mice
Colonized with normal microbiota
harvested from cecum of adult
conventionally raised mice and
fed on low fat-polysaccharide-
rich diet.
Increase in body fat content
(60%) and insulin resistance
despite reduced food intake.
Bäckhed et al., 2004
Adult germ-free
C57BL/6J mice
Transplantationof microbes taken
from the caecum of:
-obese (ob/ob) mice with greater
relative abundance of Firmicutes.
Increase in relative abundance of
Firmicutes and body fat.
Turnbaugh et al., 2008
-lean (+/+) donors with a smaller
relative abundance of Firmicutes.
Decrease in relative abundance of
Firmicutes and body fat.
Adult germ-free
C57BL/6J mice
Transplanted germ free mice with
fecal microbiota from adult
human female twin pairs;
discordant for obesity and those
mice were fed on low-fat, high
polysaccharide diet.
Mice transplanted with microbiota from an obese
twin developed higher adiposity than mice with the
microbiota from a lean twin.
Ridaura et al., 2013
Obese mice. Lean mice.
et al., 2012). In modern times (1958), fecal enemas have been
used as a cure of human pseudo-membranous colitis (Eiseman
et al., 1958). The use of GMT as a treatment for any disease,
except recurrent C. difficile (CD) infection, requires an approved
investigational new drug (IND) permit according to the US Food
and Drug Administration (FDA) (Moore et al., 2014). As such,
most studies of the effects of GMT on obesity have been limited
to mice (Table 2).
We contend that, when considering the potential efficacy of
the GMT approach for obesity, it is more appropriate to reflect
on the meta-analyses of the effectiveness of fecal transfers in
the treatment of C. difficile and inflammatory bowel disease
(Kassam et al., 2013; Colman and Rubin, 2014). Until recently,
there was no consistently effective treatment for recurrent
C. difficile infection, which leads to considerable morbidity,
including chronic diarrhea, colitis, and toxic megacolon, as
well as a reported mortality of up to 38% (Hota et al., 2012).
However, GMT is being increasingly viewed as the treatment
of choice for recurrent C. difficile infection. Moreover, meta-
analyses of clinical trials have consistently demonstrated that gut
microbiome transfer is efficacious and safe [IBD, pooled cure rate
36.2% (95% CI 17.4–60.4%); C. difficile, pooled cure rate 89.1%
(95% CI 84–93%)] (Kassam et al., 2013; Colman and Rubin,
2014). Finally, a recent study in patients with C. difficile colitis
has shown that gut microbiome transfer causes a significant shift
in composition from the diseased state to one equivalent to that
seen for healthy individuals by the human microbiome project
(Weingarden et al., 2015). As such, gut microbiome transfer holds
significant promise as a treatment for the rapid and concerted
modification of an unhealthy flora.
GMT is now being considered for a wider range of disorders,
including severe obesity and type 2 diabetes mellitus. To date,
investigation of the therapeutic benefit of GMT in adult obesity
or type 2 diabetes has been limited to a single pilot study. Vrieze
et al. performed a short-term GMT study in nine treated and nine
control middle-aged men with metabolic syndrome (Vrieze et al.,
2012), with transfer via a naso-duodenal tube. Six weeks after
GMT, treated subjects had an impressive 75% increase in insulin
sensitivity. Furthermore, GMT was associated with favorable
changes to gut microbiota that included greater bacterial diversity
and a 2.5-fold increase in butyrate-producing bacteria (Vrieze
et al., 2012). However, the study was not continued long enough
to evaluate the full potential of therapy, notably on body weight,
and composition.
Whilst gut microbiome transfer in humans offers so much
promise, it is not clear yet whether it actually leads to significant
weight loss. Moreover, the duration of the effect, treatment
composition, and mode of delivery required to achieve optimum
weight loss must be established. There are currently 17 clinical
trials registered (USA, Europe, and Australia) to test the efficacy
of GMT as a clinical treatment, mostly for C. difficile infection.
Only two of these trials are looking at GMT as a means of
treating obesity. However, the reverse effect (lean to obese) has
been demonstrated as the result of use of an overweight donor
for the treatment of recurrent C. difficile infection (Alang and
Kelly, 2015). It remains clear that there are considerable practical
and safety issues that need to be considered and overcome
before GMT can be used as a routine clinical or non-clinical
intervention (Box 2).
GMT is a promising treatment for antibiotic resistant C. difficile
infection. However, the use of GMT as a treatment for metabolic
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Jayasinghe et al. Gut Microbiome Transfer
BOX 2 | Practical and safety issues of GMT.
Choice of donor (Andrews et al., 1995; Jakobsson et al., 2010; Bakken et al., 2011; Pérez-Cobas et al., 2013; Viaud et al., 2013; Kostic et al., 2014; Panda
et al., 2014)
Related, unrelated or universal? There is debate over the relative merits of using related or unrelated donors (Bakken et al., 2011).
Once chosen, donors must be screened for: conditions associated with microbial dysbiosis (e.g., metabolic syndrome, morbid obesity, chronic fatigue
syndrome, inflammatory bowel syndrome, irritable bowel syndrome, chronic diarrhea or constipation, GI malignancy, CD toxins); intestinal pathogens (e.g.,
Giardia, Cryptosporidium, Isopora and Rotavirus, Hepatitis A, B and C, HIV, Syphilis, and Helicobater pylori); antibiotic use within the previous 3 months;
immunosuppressive treatments and anti-cancer agents; high risk-sexual behaviors; illegal drug use; recent travel to areas with endemic diarrhea, or recent
body piercings/tattoos.
Donor feces preparation (Berg et al., 1988; Lund-Tønnesen et al., 1998; Persky and Brandt, 2000; Mueller et al., 2006; Kostic et al., 2014)
The use of fresh or frozen feces.
It is unclear if the solvent (saline, non-bacteriostatic milk, yoghurt, or water), method of homogenization (hand stirring, shaking, or blender), or filtration (coffee
filter, gauze pad, or steel strainer) make a difference to transfer efficiency (Persky and Brandt, 2000; Borody et al., 2015).
There is currently no recommended standardized amount of feces suggested for use in GMT.
Route of administration and site of inoculation (Lund-Tønnesen et al., 1998; Mueller et al., 2006; Yang et al., 2009; Silverman et al., 2010; Borody and
Khoruts, 2012; Kostic et al., 2014)
Retention enemas/naso-gastric tube/naso-jejunal tube/upper tract endoscopy (esophagogastroduodenoscopy)/colonoscopy/self-administered enemas.
FIGURE 1 | Environmental and genetic interactions between the host
and the host’s microbiome impact the development and incidence of
obesity and related disorders. This relationship is also affected by diet,
exercise, psychological stress, and environmental contaminants. As such,
methods for human microbiome manipulation, including GMT, may represent a
revolutionary approach for the treatment of non-communicable diseases
including obesity.
diseases such as obesity or type 2 diabetes is only experimental
(Bäckhed et al., 2004; Turnbaugh et al., 2008; Vrieze et al., 2012;
Ridaura et al., 2013). There is still much to be learnt about the
GMT method that includes: characteristics of the ideal donor,
delivery formulation (e.g., in solution, encapsulation), mode of
administration (e.g., oral, nasojejunal, or rectal), duration of
benefit and, thus, frequency of treatment (Figure 1).
Limited data suggests that GMT is a safe treatment (Borody
and Khoruts, 2012; Vrieze et al., 2012; Van Nood et al.,
2013) that has not currently been found to be associated with
the development of new infections or diseases (Brandt et al.,
2012). Therefore, further studies are required to monitor the
long-term side-effects of GMT on both donors and recipients.
These studies should also test the theoretical and practical
benefits and side-effects of using fecal transplants as a treatment
for obesity. These include: (1) the cost, ease of intervention,
and relative safety of the non-invasive GMT as opposed to
gastric by-pass surgery and pharmaceutical interventions; (2) the
chances that GMT causes non-specific short- and long-term side-
effects similar to those caused by pharmaceutical interventions;
and (3) the psychological stress associated with the procedure
(e.g., effects of performance anxiety on the donor, Brandt,
The psychological stresses and social stigma associated
with feces mean that some patients find GMT to be an
unappealing treatment (Zipursky et al., 2012). However, a survey
of CDI patients found that regardless of GMT’s unappealing
nature, patients are willing to try it (Zipursky et al., 2012).
Whether this willingness to try GMT as a treatment would
translate to obese patients is yet to be determined. However,
if GMT is shown to be an effective treatment for obesity then
there will inevitably be greater refinement of the transplanted
microbiota into a more palatable and optimally efficacious
Frontiers in Cellular and Infection Microbiology | 7February 2016 | Volume 6 | Article 15
Jayasinghe et al. Gut Microbiome Transfer
Changes in the ratio of different gut microbial species have
been associated with onset and development of several disorders,
including obesity (Ley et al., 2005). It can be assumed that gut
microbiota impacts on host metabolism through the promotion
of increased uptake of monosaccharides, storage of triglyceride,
digestion of dietary fiber (Bäckhed et al., 2004), and synthesis
of hormonal precursors (Hartstra et al., 2014). Use of GMT to
treat several disorders (e.g., chronic C. difficile infection) has
already been established. However, it remains to be determined
if GMT may be successful also for other diseases, such as obesity
and its related complications. Based on the available evidence,
GMT may represent a novel and successful intervention that
could potentially transform the management of severe obesity in
children and adults. Randomized controlled trials are required
to confirm outcomes, efficacy and long-term safety of GMT in
the treatment of obesity. The role of specific bacteria/species
and combinations of intestinal microbiota should be clearly
addressed beyond simply the change in body fat, ideally
through longitudinal analysis of the meta-genomic, -proteomic,
and -transcriptomic composition of donor and recipient’s gut
microbial content, before and after GMT. This characterization
of GMT effects must include determining whether the process
simply changes the composition of the existing microbial
population or if it results in the complete transplantation of a
non-obese microbial population. In conclusion, GMT represents
a very real and potentially revolutionary treatment for obesity.
TJ wrote the manuscript. VC contributed to the writing of
the manuscript. DH commented on the manuscript. WC and
JO conceived, directed, and contributed to the writing of the
Work in WC and JO laboratories is funded by Gravida: National
Centre for Growth and Development. TJ is supported by a
University of Auckland Scholarship. VC is the recipient of a Pfizer
Australasian Paediatric Endocrine Care (APEC) Research Grant
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Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
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Frontiers in Cellular and Infection Microbiology | 11 February 2016 | Volume 6 | Article 15
... FMT is approved as a therapy for the treatment of recurrent infection with Clostridium difficile [45,46]. It is now under research to be used in the treatment of some other diseases like metabolic disorders [47] and hepatic encephalopathy [48]. The main benefit of the use of FMT is to restore gut health and to reverse the gut dysbiosis that is induced by either antibiotic [49] or microbial infection [50] like in the case of COVID-19 infection. ...
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Background Given the severe infection, poor prognosis, and the low number of available effective drugs, potential prevention and treatment strategies for COVID-19 need to be urgently developed. Main body Herein, we present and discuss the possible protective and therapeutic mechanisms of human microbiota and probiotics based on the previous and recent findings. Microbiota and probiotics consist of mixed cultures of living microorganisms that can positively affect human health through their antiviral, antibacterial, anti-inflammatory, and immunomodulatory effect. In the current study, we address the promising advantages of microbiota and probiotics in decreasing the risk of COVID-19. Conclusions Thus, we recommend further studies be conducted for assessing and evaluating the capability of these microbes in the battle against COVID-19.
... Moreover, FMT has been extensively studied as a potential treatment for GM-related diseases. Its effectiveness has been demonstrated in a range of diseases, such as ulcerative colitis (182), hepatic encephalopathy (183), irritable bowel syndrome (184), obesity (185), and even neurological disorders (186,187). Recent studies have revealed a correlation between epilepsy and GM; thus, the value of FMT administration in patients with epilepsy has been further investigated. ...
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The gut–brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system via neural networks and neuroendocrine, immune, and inflammatory pathways. The development of sequencing technology has evidenced the key regulatory role of the gut microbiota in several neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis. Epilepsy is a complex disease with multiple risk factors that affect more than 50 million people worldwide; nearly 30% of patients with epilepsy cannot be controlled with drugs. Interestingly, patients with inflammatory bowel disease are more susceptible to epilepsy, and a ketogenic diet is an effective treatment for patients with intractable epilepsy. Based on these clinical facts, the role of the microbiome and the gut–brain axis in epilepsy cannot be ignored. In this review, we discuss the relationship between the gut microbiota and epilepsy, summarize the possible pathogenic mechanisms of epilepsy from the perspective of the microbiota gut–brain axis, and discuss novel therapies targeting the gut microbiota. A better understanding of the role of the microbiota in the gut–brain axis, especially the intestinal one, would help investigate the mechanism, diagnosis, prognosis evaluation, and treatment of intractable epilepsy.
... It was first approved by the United States Food and Drug Administration for the treatment of Clostridium difficile infection. Fecal microbiota transplantation can modify gut microbiome for the purpose of obesity and metabolic disorders management [33,34]. Clinical studies using fecal microbiota transplantation in NAFLD subjects are currently ongoing. ...
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Nonalcoholic fatty liver disease (NAFLD) is a leading liver disease worldwide with a prevalence of approximately 25% among adult population. The highest prevalence is observed in Middle East and the lowest prevalence in Africa. NAFLD is a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Pro-inflammatory diet, overweight/obesity, inflammation, insulin resistance, prediabetes, type 2 diabetes, dyslipidemia, disrupted gut microbiome, and impaired intestinal barrier function are important risk factors associated with and/or contributing to NAFLD. Gut microbiome is a complex and diverse microbial ecosystem essential for the maintenance of human health. It is influenced by several factors including diet and medications. Gut microbiome can be disrupted in NAFLD. Intestinal epithelial barrier is the largest and most important barrier against the external environment and plays an important role in health and disease. Several factors including diet and gut microbiome impact intestinal barrier function. NAFLD can be associated with impaired intestinal barrier function (increased intestinal permeability). There are no specific drugs that directly treat NAFLD. The first-line therapy of NAFLD is currently lifestyle intervention. Weight loss is an important component in the treatment of NAFLD subjects who have excess body weight. Gut microbiome and intestinal epithelial barrier are becoming promising targets for the treatment of several diseases including NAFLD. In the absence of approved pharmacotherapy for the treatment of NAFLD/NASH, in addition to lifestyle intervention and weight loss (in case of excess body weight), focus should also be on correcting gut microbiome and intestinal permeability (directly and/or through gut microbiome modulation) using diet (e.g., low-fat diet, high-fiber diet, and Mediterranean diet), prebiotics (nondigestible food ingredients), probiotics (nonpathogenic living microorganisms), synbiotics (combination of prebiotics and probiotics), and fecal microbiota transplantation (transfer of healthy stool).
... Notably, childhood obesity is a health condition that is particularly subject to stigma; in fact, healthcare professionals report not raising the topic for fear of damaging their relationships with families [32]. Given the association between obesity and imbalance of the gut microbiome [33], interventions such as vaginal seeding -which was largely viewed in a positive or neutral light by our questionnaire respondents -could have the potential to help with its prevention, without placing primary focus on the condition itself. ...
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Background Vaginal seeding is the administration of maternal vaginal bacteria to babies following birth by caesarean section (CS), intended to mimic the microbial exposure that occurs during vaginal birth. Appropriate development of the infant gut microbiome assists early immune development and might help reduce the risk of certain health conditions later in life, such as obesity and asthma. We aimed to explore the views of pregnant women on this practice. Methods We conducted a sequential mixed-methods study on the views of pregnant women in New Zealand (NZ) on vaginal seeding. Phase one: brief semi-structured interviews with pregnant women participating in a clinical trial of vaginal seeding ( n = 15); and phase two: online questionnaire of pregnant women throughout NZ (not in the trial) ( n = 264). Reflexive thematic analysis was applied to interview and open-ended questionnaire data. Closed-ended questionnaire responses were analysed using descriptive statistics. Results Six themes were produced through analysis of the open-ended data: “seeding replicates a natural process”, “microbiome is in the media”, “seeding may have potential benefits”, “seeking validation by a maternity caregiver”, “seeding could help reduce CS guilt”, and “the unknowns of seeding”. The idea that vaginal seeding replicates a natural process was suggested by some as an explanation to help overcome any initial negative perceptions of it. Many considered vaginal seeding to have potential benefit for the gut microbiome, while comparatively fewer considered it to be potentially beneficial for specific conditions such as obesity. Just under 30% of questionnaire respondents ( n = 78; 29.5%) had prior knowledge of vaginal seeding, while most ( n = 133; 82.6%) had an initially positive or neutral reaction to it. Few respondents changed their initial views on the practice after reading provided evidence-based information ( n = 60; 22.7%), but of those who did, most became more positive ( n = 51; 86.4%). Conclusions Given its apparent acceptability, and if shown to be safe and effective for the prevention of early childhood obesity, vaginal seeding could be a non-stigmatising approach to prevention of this condition among children born by CS. Our findings also highlight the importance of lead maternity carers in NZ remaining current in their knowledge of vaginal seeding research.
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Epidemiological and associative research from humans and animals identifies correlations between the environment and health impacts. The environment-health inter-relationship is effected through an individual's underlying genetic variation and mediated by mechanisms that include the changes to gene regulation that are associated with the diversity of phenotypes we exhibit. However, the causal relationships have yet to be established, in part because the associations are reduced to individual interactions and the combinatorial effects are rarely studied. This problem is exacerbated by the fact that our genomes are highly dynamic; they integrate information across multiple levels (from linear sequence, to structural organisation, to temporal variation) each of which is open to and responds to environmental influence. To unravel the complexities of the genomic basis of human disease, and in particular non-communicable diseases that are also influenced by the environment (e.g., obesity, type II diabetes, cancer, multiple sclerosis, some neurodegenerative diseases, inflammatory bowel disease, rheumatoid arthritis) it is imperative that we fully integrate multiple layers of genomic data. Here we review current progress in integrated genomic data analysis, and discuss cases where data integration would lead to significant advances in our ability to predict how the environment may impact on our health. We also outline limitations which should form the basis of future research questions. In so doing, this review will lay the foundations for future research into the impact of the environment on our health.
Introduction: Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC. Methods: One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations. Results: Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect. Conclusion: Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.
The prevalence of metabolic syndrome (MetS) and dyslipidemia and associated cardiovascular diseases risk factors such as obesity, diabetes, and hypertension is now a global epidemic. Although these metabolic diseases’ complex pathophysiology is one of the significant hurdles in developing preventive and/or therapeutic strategies, some factors are or can be speculated to be more useful to target than others. Natural nondigestible polysaccharides from various sources are considered potent modulators of the gut microbiome and these metabolic disorders. Recently, studies are being carried out on novel polysaccharides and their application as functional components to modulate the gut microbiome composition to improve the host’s health, including MetS. Therefore as prebiotic components, polysaccharides are being speculated to confer positive effects in managing metabolic diseases like obesity and diabetes. This chapter discussed the polysaccharides and their impacts on metabolic health and how they could help prevent or lessen metabolic diseases such as obesity, type 2 diabetes, hypertension, and dyslipidemia.
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Background Donor selection is an important factor influencing the engraftment and efficacy of fecal microbiota transplantation (FMT) for complex conditions associated with microbial dysbiosis. However, the degree, variation, and stability of strain engraftment have not yet been assessed in the context of multiple donors. Methods We conducted a double-blinded randomized control trial of FMT in 87 adolescents with obesity. Participants were randomized to receive multi-donor FMT (capsules containing the fecal microbiota of four sex-matched lean donors) or placebo (saline capsules). Following a bowel cleanse, participants ingested a total of 28 capsules over two consecutive days. Capsules from individual donors and participant stool samples collected at baseline, 6, 12, and 26 weeks post-treatment were analyzed by shotgun metagenomic sequencing allowing us to track bacterial strain engraftment and its functional implications on recipients’ gut microbiomes. Results Multi-donor FMT sustainably altered the structure and the function of the gut microbiome. In what was effectively a microbiome competition experiment, we discovered that two donor microbiomes (one female, one male) dominated strain engraftment and were characterized by high microbial diversity and a high Prevotella to Bacteroides (P/B) ratio. Engrafted strains led to enterotype-level shifts in community composition and provided genes that altered the metabolic potential of the community. Despite our attempts to standardize FMT dose and origin, FMT recipients varied widely in their engraftment of donor strains. Conclusion Our study provides evidence for the existence of FMT super-donors whose microbiomes are highly effective at engrafting in the recipient gut. Dominant engrafting male and female donor microbiomes harbored diverse microbial species and genes and were characterized by a high P/B ratio. Yet, the high variability of strain engraftment among FMT recipients suggests the host environment also plays a critical role in mediating FMT receptivity. Trial registration The Gut Bugs trial was registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12615001351505 ). Trial protocol The trial protocol is available at .
Metabolic disorders such as obesity are a serious health issue causing various health impairments, including cardiovascular diseases, type-2 diabetes, musculoskeletal disorders and several types of cancer. Recent studies have shown that there is a correlation between gut microbiota and metabolic disorders. It was revealed that differences in composition of intestinal microbiota are noticeable between lean and obese subjects. The gut microbes impact the metabolism of the host as well as immunological and endocrine systems. These microorganisms can regulate gene expression which can influence the host’s ability to store or obtain energy from edible products. Therefore, it is essential to maintain proper balance of intestinal microbiota, by proper diet and usage of probiotics and prebiotics, in order to keep the host’s health intact. The impact of gastrointestinal microbes, probiotics, and prebiotics on several processes leading to abovementioned metabolic disorder is further discussed giving a clear overview on the subject.
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Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases.
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The number of prokaryotes and the total amount of their cellular carbon on earth are estimated to be 4–6 × 1030 cells and 350–550 Pg of C (1 Pg = 1015 g), respectively. Thus, the total amount of prokaryotic carbon is 60–100% of the estimated total carbon in plants, and inclusion of prokaryotic carbon in global models will almost double estimates of the amount of carbon stored in living organisms. In addition, the earth’s prokaryotes contain 85–130 Pg of N and 9–14 Pg of P, or about 10-fold more of these nutrients than do plants, and represent the largest pool of these nutrients in living organisms. Most of the earth’s prokaryotes occur in the open ocean, in soil, and in oceanic and terrestrial subsurfaces, where the numbers of cells are 1.2 × 1029, 2.6 × 1029, 3.5 × 1030, and 0.25–2.5 × 1030, respectively. The numbers of heterotrophic prokaryotes in the upper 200 m of the open ocean, the ocean below 200 m, and soil are consistent with average turnover times of 6–25 days, 0.8 yr, and 2.5 yr, respectively. Although subject to a great deal of uncertainty, the estimate for the average turnover time of prokaryotes in the subsurface is on the order of 1–2 × 103 yr. The cellular production rate for all prokaryotes on earth is estimated at 1.7 × 1030 cells/yr and is highest in the open ocean. The large population size and rapid growth of prokaryotes provides an enormous capacity for genetic diversity.
Although we might shudder at the thought of billions of bacteria living in our lower intestine, we are colonized by these passengers shortly after birth. However, the relationship is mostly of mutual benefit, and they shape our immune system throughout life. Here, we describe our developing understanding of the far-reaching effects that the commensal flora have on mucosal and systemic immunity and their relevance to the effects of hygiene on human disease.
Background: Despite the effectiveness of fecal microbiota transplantation (FMT) for treating recurrent Clostridium difficile (C. difficile) infection, some patients are reluctant to accept this therapy. Our study examined attitudes towards FMT and factors that contribute to patients' acceptance of this treatment. Methods: We distributed patient surveys at a Veterans Affairs hospital, a public hospital, and an academic faculty practice. Multivariable logistic regression was performed, adjusting for factors associated with FMT acceptance on univariate analysis and prior experience with C. difficile infection. Results: Of 267 patients, only 12% knew of FMT prior to the survey, but 77% would undergo the procedure if medically indicated. On multivariable analysis, those with children and with college degrees or higher were more likely to agree to FMT (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.02-4.35; OR 2.27, 95% CI 1.11-4.60 respectively). Sixty-five respondents (71%) chose colonoscopy as the preferred vehicle for FMT, while nasogastric tube was least preferred. Disease transmission was the most common concern (30%, n=242), and FMT success rate was the least selected concern (9.1%). Conclusions: Most patients in a diverse sample of gastroenterology clinics had no prior knowledge of FMT, but were receptive to the procedure. Having children and higher education levels were predictors for FMT acceptance. Our findings suggest that barriers to FMT utilization may be overcome with counseling about safety concerns. More data on the risk of transmitting diseases or clinical characteristics, such as obesity, through FMT are needed and will be important for the acceptance of this procedure.
Aim: To study the role of intestinal flora in inflammatory bowel disease (IBD). Methods: The spatial organization of intestinal flora was investigated in normal mice and in two models of murine colitis using fluorescence in situ hybridization. Results: The murine small intestine was nearly bacteria-free. The normal colonic flora was organized in three distinct compartments (crypt, interlaced, and fecal), each with different bacterial compositions. Crypt bacteria were present in the cecum and proximal colon. The fecal compartment was composed of homogeneously mixed bacterial groups that directly contacted the colonic wall in the cecum but were separated from the proximal colonic wall by a dense interlaced layer. Beginning in the middle colon, a mucus gap of growing thickness physically separated all intestinal bacteria from contact with the epithelium. Colonic inflammation was accompanied with a depletion of bacteria within the fecal compartment, a reduced surface area in which feces had direct contact with the colonic wall, increased thickness and spread of the mucus gap, and massive increases of bacterial concentrations in the crypt and interlaced compartments. Adhesive and infiltrative bacteria were observed in inflamed colon only, with dominant Bacteroides species. Conclusion: The proximal and distal colons are functionally different organs with respect to the intestinal flora, representing a bioreactor and a segregation device. The highly organized structure of the colonic flora, its specific arrangement in different colonic segments, and its specialized response to inflammatory stimuli indicate that the intestinal flora is an innate part of host immunity that is under complex control.
STUDY QUESTION What are the summary effects of bariatric surgery compared with non-surgical treatment for obesity on body weight loss, comorbidities, adverse events, and quality of life? SUMMARY ANSWER Bariatric surgery is more effective in inducing body weight loss and remission of type 2 diabetes and metabolic syndrome after a maximal follow-up of 2 years, no cardiovascular events or deaths were reported after bariatric surgery, and the most common adverse events after bariatric surgery were iron deficiency anaemia and reoperations.