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Fecal Microbiota Transplantation for Fibromyalgia: A Case Report and Review of the Literature

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Abstract

A 58-year-old patient diagnosed with fibromyalgia, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS), non-responsive to variety of treatments over the years, suffered from significant social and occupational disabilities. The patient was interested in fecal microbiota transplantation (FMT), but given that FMT is not approved for these indications, he used an online protocol for FMT screening and preparation and self-instilled the filtrate using an enema 6 times. FMT resulted in a gradual improvement of symptoms and 9 months after the last treatment, the patient reported full recovery of symptoms, going back to work at full time employment. Improvement of symptoms was associated with major alterations of the enteric microbiota, according to next generation sequencing analysis performed before the first FMT and after the last FMT. Most prominent alterations at the genus level included a decrease in fecal Streptococcus proportion from 26.39% to 0.15% and an increase in Bifidobacterium from 0% to 5.23%. This case is added to several additional case reports that demonstrated the effectivity of FMT in these functional disorders that are lacking an otherwise good medical therapeutic intervention. We conclude that randomized controlled trials are required to ground FMT as a possible therapy for these difficult-to-treat conditions.
Open Journal of Gastroenterology, 2017, 7, 131-139
http://www.scirp.org/journal/ojgas
ISSN Online: 2163-9469
ISSN Print: 2163-9450
DOI: 10.4236/ojgas.2017.74015 April 28, 2017
Fecal Microbiota Transplantation for
Fibromyalgia:
A Case Report and Review of the Literature
T. Thurm1, J. N. Ablin2, D. Buskila3,4, N. Maharshak1*
1The Bacteriotherapy Clinic, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Affiliated to
the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
2Institute of Rheumatology, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv,
Israel
3Department of Medicine H, Soroka Medical Center, Beer Sheva, Israel
4Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
Abstract
A 58-year-old patient diagnosed with fibromyalgia, irritable
bowel syndrome
(IBS) and chronic fatigue syndrome (CFS), non-
responsive to variety of
treatments over the years, suffered from significant social and occupational
disabilities. The patient was interested in fecal microbiota transplantation
(FMT), but give
n that FMT is not approved for these indications, he used an
online protocol for FMT screening and preparation and self-instilled the fi
l-
trate using an enema 6 times. FMT resulted in a gradual improvement of
symptoms and 9 months after the last treatment, the patient reported full r
e-
covery of symptoms, going back to work at full time employment. Improv
e-
ment of symptoms was associated with major alterations of the enteric micr
o-
biota, according to next generation sequencing analysis performed before the
first FMT and after the last FMT. Most prominent alterations at the genus
level included a decrease in fecal
Streptococcus
proportion from 26.39% to
0.15% and an increase in
Bifidobacterium
from 0% to 5.23%. This case is
added to several additional case reports
that demonstrated the effectivity of
FMT in these functional disorders that are lacking an otherwise good medical
therapeutic intervention. We conclude that randomized controlled trials are
required to ground FMT as a possible therapy for these difficult-to-treat co
n-
ditions.
Keywords
Microbiota, Microbiome, Irritable Bowel Syndrome, Functional Disorders,
Dysbiosis, Chronic Fatigue Syndrome
How to cite this paper:
Thurm, T., Ablin,
J
.N., Buskila, D. and Maharshak, N. (2017
)
Fecal Microbiota Transplantation for F
i-
bromyalgia: A Case Report and Review of
the Literature
.
Open Journal of Gastroe
n-
terology
,
7
, 131-139.
https://doi.org/10.4236/ojgas.2017.74015
Received:
February 25, 2017
Accepted:
April 25, 2017
Published:
April 28, 2017
Copyright © 201
7 by authors and
Scientific
Research Publishing Inc.
This work is licensed under the Creative
Commons Attribution
International
License (CC BY
4.0).
http://creativecommons.org/licenses/by/4.0/
Open Access
T. Thurm et al.
132
1. Case Presentation
A 58-year-old patient presented to our outpatient clinic complaining of severe
diffuse pain, insomnia, diarrhea, abdominal pain, bloating, photophobia, hyper-
sensitivity to odor, noise, light touch, tinnitus and palpitations. He suffered from
cognitive impairment: memory loss, concentration deficit and depression with
suicidal thoughts.
Most of his symptoms started 18 years earlier at the age of 40. He was diag-
nosed with fibromyalgia, IBS and CFS. On his physical examination, typical
tender points for fibromyalgia were accessed. He underwent lactose, glucose,
fructose and sorbitol breath tests, stool cultures, serological testing for inflam-
matory bowel disease and celiac, fecal calprotectin level test, upper endoscopy
and colonoscopy. As all 4 breath tests were positive, the patient was diagnosed
with small intestinal bacterial overgrowth (SIBO). ASCA IgA was also mildly
positive and he underwent a video capsule endoscopy that was normal.
Throughout the years, the patient was treated with selective serotonin reup-
take inhibitors (SSRIs), serotonin antagonist and reuptake inhibitors (SARIs),
serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepres-
sants (TCAs), gamma-aminobutyric acid (GABA), pregabalin, tramadol, Omega
3, Cognitive Behavioral Therapy (CBT), medical cannabis, St. Johns wort
(
Hypericum perforatum
), acupuncture, medicinal hot springs, hydrotherapy,
mild exercise, all without considerable effect.
After a personal tragedy, the disease progressed and the patient became dis-
abled and stopped working. He spent most of his days in bed, unable to perform
minimal physical activity; his insomnia has worsened despite treatment with
melatonin and sleeping pills. Memory impairment had become severe, with
memory loss of close relatives and friends, and marked disorientation. Social
security has granted the patient 70% general disability and a complete (100%)
occupational disability.
The patient sent his own stool samples for microbial next generation sequ-
encing analysis at a commercial lab. The results demonstrated high levels of
Streptococci
(Table 1). Stool culture, done at the same time, was positive for
Candida
. He was treated with Hydroxychloroquine and Rifampicin, VSL#3
(probiotic), dietary change to low carbohydrates and low sugar diet, reporting
mild and short standing improvement.
The patient was interested in FMT as an experimental treatment for his mixed
symptoms caused by fibromyalgia, CFS and IBS. Given that this type of treat-
ment is not approved for these indications, he used an online protocol for FMT
screening and preparation. His son was screened for HIV, HCV, fecal parasites
and bacterial cultures. Stool was homogenized with a food processor and was
self-instilled using an enema. Within 24 hours he experienced dramatic im-
provement of symptoms that lasted for 6 weeks. Four consecutive FMTs resulted
with the same transient improvement of symptoms, lasting for approximately 6
weeks each. The improvement from the sixth course lasted for over 9 months
and included additional treatment for SIBO with FODMAP and rifaximin.
T. Thurm et al.
133
Table 1. Fecal microbiota analysis performed prior and post fecal microbial transplan-
tation (FMT). A 16S rDNA genome sequencing demonstrating microbial composition
alterations at the “Genus levelfollowing FMT.
Phylum Family Genus
% of total
(Pre FMT)
% of total
(Post FMT)
Firmicutes
(gram+)
Lachnospiraceae Anaerostipes 7.92* 0.09
0.72
1.66
6.85
0.61
Moryella 0 0
Roseburia 32.11 3.01
Sporobacterium 0 0
Syntrophococcus 0 0
Ruminococcaceae Acetanaerobacterium 0 0
Acetivibrio 1.22* 0
Ethanoligenens 0 0
Faecalibacterium 0.08 5.65
Papillibacter 0 0
Ruminococcus 1.27* 4.51
Sporobacterium 0 0
Subdoligranulum 0.17 0
Clostridiaceae Butyricicoccus 0 0
Clostridium 0 1.58
Lactonifactor 0.08* 0
Eubacteriaceae Naaerofustis 0 0
Eubacterium 0 4.91*
Blautia Blautia 21.51 10.92
Howardella Howardella 0 0
Lactobacillaceae Lactobacillus 0.2 0.25
Enterococcaceae Enterococcus 0 0.03*
Streptococcaceae Lactococcus 0 0
Streptococcus 26.39* 0.15
Leuconostocaceae Leuconostoc 0 0.01
Erysipelotrichaceae Catenibacterium 0 0
Coprobacillus 0.54 0.5
Holdemania 0 0
Turicibacter 0* 0.04*
Veillonellaceae
0
0
0
0
0
2.26*
Oscillospiaceae Oscillibacter 0.29 0
Staphlococcaceae Staphylococcus 0 0
Bacteroidetes
(gram−)
Bacteroidaceae Bacteroides 0.42 21.11*
Rikenellaceae Alistipes 0 0
Porphyromonadaceae Barnesiella 0 0
Odoribacter 0 0.04
Parabacteroides 0 1.04
T. Thurm et al.
134
Continued
Prevotellaceae Prevotella 0 17.64*
Xylanibacter 0 0
Actinobacteria
(gram+)
Bifidobacteriaceae Bifidobacterium 0* 5.23
Actinomycetaceae Actinomyces 0 0.01
Micrococcineae Rothia 0 0
Coriobacteriaceae Asaccharobacter 0* 0*
Collinsella 0 6.73
Olsenella 0 0
Slackia 0 1.47*
Proteobacteria
(gram−)
Enterobacteriaceae Escherichia/Shigella 0 0.45
Klebsiella 0 0
Sutterellaceae Cutterella 0 0.31
Desulfovibrionaceae Lawsonia 0 0
*Abnormal % of total microbiota as defined by the reference of the commercial lab.
The patient reported marked improvement with total resolution of fatigue and
depression, marked improvement of insomnia, oversensitivity to touch, odor
and noise. Cognitive impairment has also improved. A physical examination by
a rheumatologist (JN A) was normal with no evidence of synovitis or tender fi-
bromyalgia points, concluding that all his symptoms had improved. The patient
returned to full employment and is now asymptomatic for over a year.
A second stool microbial analysis demonstrated significant changes compared
to the first analysis (Table 1, Table 2). Most marked was a decrease in the propor-
tion of the Firmicutes phylum from 99.35% to 36.17% and an increase in the Bac-
teriodetes phylum from 0.42% to 39.82% post FMT. At the genus level, fecal
Streptococcus
proportion fell from 26.39% to 0.15% and
Bifidobacterium
in-
creased from 0% to 5.23%. Additional changes included bacterial diversity index
that was reduced from 3.21 to 2.55 post FMTs and a negative stool culture for
Candida.
2. Discussion
Functional disorders, such as fibromyalgia, CFS and IBS, affect many patients
and are frequently associated. These disorders clinically differ with an unclear
pathogenesis.
Fibromyalgia affects up to 2% of general population [1]. Pain is a predomi-
nant symptom of fibromyalgia. However, fatigue, non-refreshed sleep, mood
disturbance and cognitive impairment are common, and have an important in-
fluence on quality of life [2]. The European league against Rheumatism (EUL-
AR) recommendations, for the management of fibromyalgia were published in
2016: Graduated approach aiming at improving health-related quality of life by
non-pharmacological modalities is advised as first line therapy [3].
CFS is diagnosed after at least 6 months of unexplained fatigue [4]. CBT and
graded exercise therapy (GET) have shown moderate effectiveness [5].
T. Thurm et al.
135
Table 2. Fecal microbiota analysis performed prior and post fecal microbial transplan-
tation (FMT). A 16S rDNA genome sequencing demonstrating microbial composition
alterations at thePhylumand Familylevel following FMT.
% Pre FMT % Post FMT
Firmicutes 99.35 36.17
Lachnospiraceae
47.6 5.37
Ruminococcaceae
2.74 10.16
Clostridiaceae
0.08 1.58
Bacteroidetes 0.42 39.82
Actinobacteria 0 13.44
Proteobacteria 0 0.76
IBS is a functional disorder characterized by abdominal pain or discomfort
associated with defecation or change in bowel habits according the Rome criteria
[6]. IBS usually causes long-term symptoms, which may occur in episodes. The
symptoms interfere with daily life and social functioning in many patients. The
prevalence of IBS in Europe and North America is estimated to be 10% to 15%
[7].
There is a marked overlap between these conditions. The prevalent theory
suggests that CNS dysfunction of unknown origin causes over responsiveness to
sensory perception stimuli that are within the normal range among healthy indi-
viduals in patients suffering from fibromyalgia, CFS, IBS and other functional
disorders [8]. Investigations using standardized criteria reported 42% - 70% of
fibromyalgia patients meeting IBS criteria [9] [10] and one study demonstrated
92% IBS in patients diagnosed with CFS [11]. Many patients report being diag-
nosed with fibromyalgia and later the diagnosis is converted to CFS and vice
versa.
During the last decade, the importance of the enteric microbiome for health
and disease conditions has emerged. Changes in the composition of gut micro-
biota (dysbiosis), have been associated with gastrointestinal, metabolic, autoi-
mmune, allergic and neuropsychiatric disorders [12] and specifically in IBS pa-
tients [13] [14], fibromyalgia [14] and in CFS [15]. Moreover, interventions al-
tering the enteric microbiota, such as probiotics therapy [16], and rifaximin [17]
have shown efficacy in IBS patients.
FMT, which is the infusion of liquid filtrate feces from a healthy donor, into
the gut of an affected recipient, has shown significant benefit for the treatment of
Clostridium difficile
infection (CDI) [18] [19] and is currently the recommend-
ed therapy for recurrent CDI [20]. FMT has also shown positive results for the
treatment of inflammatory bowel disease [21] in multiple studies and have
demonstrated some efficacy in non GI disorders, such as in Parkinson’s disease
[22], myoclonus dystonia [23], multiple sclerosis [24], obesity, insulin resistance
and metabolic syndrome [25]. In a study of 60 CFS patients treated with FMT,
response rate was 70%. Twelve of the patients were contacted after 15 - 20 years,
7 reported full recovery and 5 reported no CFS symptoms for 1.5 and 3 years
T. Thurm et al.
136
following FMT [26].
In IBS patients, few studies, mostly case reports and case series, have demon-
strated positive results for FMT [27] and it is currently tested in randomized
controlled trials [NIH. clinical trialNCT02328547].
D-lactic acid producing
Enterococcus
and
Streptococcus
species were shown
to be over-represented in CFS patients [28]. A recent study comparing microbi-
ota of CFS patient to controls, observed significantly lower levels of
Faecalibac-
terium
and
Bifidobacterium
in the CFS population compared to healthy controls
[15].
Faecalibacterium
is known to have anti-inflammatory properties [29] and
Bifidobacterium
, commonly used as probiotics [30], was previously reported to
reduce CRP levels in a cohort of CFS patients [31]. In addition, a significantly
higher load of
Candida albicans
was found in CFS patients when in the acute
phase of illness compared with when in remission [32]. Although the clinical
significance of these findings is yet to be determined and although the fecal mi-
crobial analysis was not performed as a part of a clinical trial, some of the mi-
crobial alterations cited above are in line with the microbial alterations observed
before and after FMT in our case. Specifically, the decrease of fecal
Streptococcus
and increased
Bifidobacterium
proportions and loss of fecal
Candida
, may sup-
port the beneficial properties of FMT.
Nevertheless, our results should be interpreted with caution, given that in ad-
dition to self FMTs, the patient underwent multiple additional interventions
such as different dietary regiments, therapeutic trials with multiple medications,
antibiotics and probiotics. These can also be responsible, at least partially, for the
microbial alterations that were found, such as the decreased microbial diversity
index that dropped from 3.21 to 2.55 perhaps due to antibiotics treatment.
Moreover, as in any treatment modality implemented for chronic pain, a sig-
nificant placebo response must also be taken under consideration. However, the
clinical improvement was clearly associated with the FMTs treatments.
No RCTs or case series have been published on FMT for fibromyalgia. To our
knowledge, this is the first case of self-executed FMT resulting in full recovery of
fibromyalgia and CFS. In the absence of satisfactory cognitive or pharmacologi-
cal treatment for these disorders, few publications reported the experience of
FMT for these indications.
Although there are no randomized control trials (RCTs) supporting this
treatment, in a few case series on CFS and reports on fibromyalgia, FMT in-
duced long term remission of CFS [26] and could be beneficial for fibromyalgia.
This is a low risk procedure with mostly mild and short term complications [33]
[34], with possible long term remission that may result in a significant cost ef-
fectiveness. A major concern is that the fame of FMT may lead patients to use a
“do-it-yourself” approach (as in this case), without medical supervision, with
possibly harmful consequences [35] [36]. A case of UC patient who suffered cy-
tomegalovirus infection after performing FMT without donor screening was re-
ported [37] and therefore we do not support performing FMT without appro-
priate medical care.
T. Thurm et al.
137
3. Conclusions
We have described a case of self-performed FMT, in which FMT was extremely
beneficial in a severely ill patient who suffered from a combination of three
functional disorders-fibromyalgia, CFS and IBS. The patient had high levels of
Candida
and
Streptococci
that have normalized after the FMT.
We conclude that FMT should be tested as a possible treatment for fibromyal-
gia and CFS. Controlled data regarding the microbiome characteristics of pa-
tients suffering from fibromyalgia should be obtained, and RCTs are required to
ground FMT as a possible therapy for these difficult-to-treat conditions, to learn
whether this approach is truly beneficial, who is the right target population, who
should serve as donors and what is the right protocol of performing FMT for
this patient population: number of FMTs, volume and optimal way of adminis-
tration.
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... 179 A patient with fibromyalgia, with a predominant symptom of pain, was reported to be in full recovery after FMT. 180 In this study, the most prominent changes at the genus level included an increase in faecal Bifidobacterium proportion from 0% to 5.23% and a reduction in Streptococcus from 26.39% to 0.15%. 180 Moreover, because colonic supernatants from chronic morphine exposure induced acute tolerance and neuronal hyperexcitability in naïve DRG neurones, engraftment of microbiota competing with indigenous gut microbiota may prevent or delay the development of morphine tolerance. ...
... 179 A patient with fibromyalgia, with a predominant symptom of pain, was reported to be in full recovery after FMT. 180 In this study, the most prominent changes at the genus level included an increase in faecal Bifidobacterium proportion from 0% to 5.23% and a reduction in Streptococcus from 26.39% to 0.15%. 180 Moreover, because colonic supernatants from chronic morphine exposure induced acute tolerance and neuronal hyperexcitability in naïve DRG neurones, engraftment of microbiota competing with indigenous gut microbiota may prevent or delay the development of morphine tolerance. 181 Several mechanisms underlying the therapeutic effects of FMT on chronic pain were proposed, including direct competition of pathogenic bacteria with commensal microbiota, protection of the intestinal barrier, restoration of secondary BA metabolism, and stimulation of the intestinal immune system. ...
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The relationship between gut microbiota and neurological diseases, including chronic pain, has received increasing attention. The gut microbiome is a crucial modulator of visceral pain, whereas recent evidence suggests that gut microbiota may also play a critical role in many other types of chronic pain, including inflammatory pain, headache, neuropathic pain, and opioid tolerance. We present a narrative review of the current understanding on the role of gut microbiota in pain regulation and discuss the possibility of targeting gut microbiota for the management of chronic pain. Numerous signalling molecules derived from gut microbiota, such as by-products of microbiota, metabolites, neurotransmitters, and neuromodulators, act on their receptors and remarkably regulate the peripheral and central sensitisation, which in turn mediate the development of chronic pain. Gut microbiota-derived mediators serve as critical modulators for the induction of peripheral sensitisation, directly or indirectly regulating the excitability of primary nociceptive neurones. In the central nervous system, gut microbiota-derived mediators may regulate neuroinflammation, which involves the activation of cells in the blood-brain barrier, microglia, and infiltrating immune cells, to modulate induction and maintenance of central sensitisation. Thus, we propose that gut microbiota regulates pain in the peripheral and central nervous system, and targeting gut microbiota by diet and pharmabiotic intervention may represent a new therapeutic strategy for the management of chronic pain.
... FMT is one of the main tools to manipulate the microbiome composition. FMTs are used as an emerging treatment for a wide range of disorders, including Parkinson's disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism [66,67,68,69,70,71,72,73]. However, there are many open questions in FMT, including donor selection and screening, standardized protocols, long-term safety, and regulatory issues. ...
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Background Some microbiome composition can be associated with negative outcomes, including among others, obesity, disease and the failure to respond to treatment. Microbiota manipulation or supplementation have been argued to restore the microbiome associated with a healthy condition. Fecal Microbiota Transplantation (FMT) is among the most popular microbiome intervention procedures. Current practices are to choose the transplanted microbiome based on the donor phenotype, and not based on the expected recipient phenotype. However, the two differ drastically. We here propose an algorithm to predict the expected outcome of FMT from the donor phenotype, and optimize the FMT for different required outcomes. Results We here show, using multiple microbiome properties, that the donor and recipient phenotypes differ widely, and propose a tool to predict the recipient phenotype after the FMT using only the donors' microbiome and when available demographics for transplants from humans to either antibiotic treated mice, or other humans. We then extend the method to optimize the best-planned transplant (bacterial cocktails) by combining the predictor and a genetic algorithm (GA). We validate the predictor using a de-novo FMT experiment highlighting the possibility to choose transplants that optimize an array of required goals. We further show that a limited number of taxa is enough to produce an optimal FMT. Conclusions Over the shelf FMT require recipient independent optimized FMT selection. Such a transplant can be from an optimal donor, or from a cultured set of microbes. We have here shown the feasibility of both types of donations in antibiotic treated mice and for transplants between humans.
... While there was a 26% decrease in fecal Streptococcus species, a 5% increase was found in Bifidobacteria species. [51] Amyloid and Tau protein pathology in the brain was reduced after FMT was administered to mice experiencing Alzheimer's-like symptoms. [52] An increase in cognition and a decrease in systemic inflammation have been reported with this change. ...
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Article
Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy, fecal transfusion, and stool transplantation, is considered to be one of the remarkable treatments of the last century. Fecal microbiota transplantation is the process of filtering and diluting the stool from a healthy donor and placing it in the gastrointestinal tract of the recipient. It was first used orally in the fourth century, under the name of "Yellow Soup" in China for food poisoning and diarrhea. Recently, it has been widely used in various clinical situations, recurrent and resistant cases of Clostridium difficile bacterial infection. The purpose of the FMT procedure is to improve the intestinal flora by suppressing the deteriorated intestinal microbiota with a healthy bacterial community. In this review, how to treat diseases with FMT and the positive effects of this method on patients with neurological disorders, allergy and cancer were discussed.
... Bağırsak mikrobiyotası ile insan fizyolojisi arasındaki bağlantı düşünüldüğünde çoğu hastalığın sağlıklı bağırsak mikrobiyotasının bozulması sonucu ortaya çıktığı öne sürülmektedir 15 . Literatürde bağırsak mikrobiyotasının bileşimindeki değişikliklerin gastrointestinal, metabolik, otoimmün, alerjik ve nöropsikiyatrik bozukluklarla ilişkili olduğu birçok çalışmada gösterilmiştir 16 . ...
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Fibromyalgia syndrome (FMS) is one of the most frequent forms of chronic widespread pain, with a reported prevalence of 3-10% in the adult population. Clinical presentation of the typical pain and the presence of associated somatic and psychological symptoms form the basis of the diagnosis. FMS is associated with nervous system dysfunction and neurotransmitters act as targets of a number of drugs approved for fibromyalgia. However, although the underlying mechanisms in FMS are not yet known precisely, many hypotheses have been put forward. Considering the relation between fibromyalgia and irritable bowel syndrome (IBS), altered gut microbiome could be associated with fibromyalgia. In this study, it was aimed to investigate the variation of intestinal microbiome levels in patients with FMS compared to healthy controls. For the investigation of the microbiome, fecal samples were collected from a cohort of 54 patients with FMS and 36 healthy individuals. Those with any mental and/or physical illness in the control group were excluded from the study. The FMS patient group was determined according to the "American College of Rheumatology (ACR)" 2010 diagnostic criteria. The fecal samples were stored at -80°C until use and were thawed on ice; for each extraction, 0.3 g of faeces were weighed. Extraction of DNA was carried out with commercial kit according to the manufacturer's recommendations. Samples were compared using 16S rRNA gene amplification with specific primers of Bacteroidetes, Firmicutes, Enterobacter, Lactobacillus, Streptococcus and Bifidobacterium by the real-time PCR method. According to our results, while the increase of Bacteroidetes and Bifidobacterium was statistically significant (p<0.05), Firmicutes decreased (p<0.001) in the patient group. No statistically significant results were found for Enterobacter, Streptococcus and Lactobacillus (p> 0.05). When the relationship between bacteria was evaluated, a high statistically significance and negative correlation was found between Bacteroidetes and the percentage of Firmicutes (r= -0.778, p<0.001),while a moderate statistical significance and positive correlation was observed between the percentage of Enterobacter and Bifidobacterium (r= 0.460, p= 0.005). The results suggest that the gut microbiota may play a role in fibromyalgia. The balance of Firmicutes and Bacteroidetes phyla in the gut is known to have important effects on intestinal homeostasis. In summary, it is clear that large-scale further research in larger cohorts will be effective in understanding the relationship between the gut microbiome and FMS and evaluating possible treatment options.
... Recently, the restoration of gut microbiota to the predisease state has become a vital novel treatment, and the new trend of FMT has been used to cure several diseases, such as ulcerative colitis [138] and Clostridium difficile infection [139]. Surprisingly, it is reported that a patient diagnosed with fibromyalgia completely recover after the fecal microbiota transplantation [140], making chronic refractory pain-related diseases a potential therapeutic indication of the treatment. Although fibromyalgia is excluded from the diagnosis of NP since 2011, the pathophysiology of fibromyalgia includes small fiber neuropathy, suggesting a partial overlap between the two pathogeneses. ...
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Article
Abstract Neuropathic pain (NP) is a sustained and nonreversible condition characterized by long-term devastating physical and psychological damage. Therefore, it is urgent to identify an effective treatment for NP. Unfortunately, the precise pathogenesis of NP has not been elucidated. Currently, the microbiota-gut-brain axis has drawn increasing attention, and the emerging role of gut microbiota is investigated in numerous diseases including NP. Gut microbiota is considered as a pivotal regulator in immune, neural, endocrine, and metabolic signaling pathways, which participates in forming a complex network to affect the development of NP directly or indirectly. In this review, we conclude the current understanding of preclinical and clinical findings regarding the role of gut microbiota in NP and provide a novel therapeutic method for pain relief by medication and dietary interventions.
... Furthermore, there is emerging experimental evidence that changing the gut microbiome through probiotics (Lactobacillus casei Shirota (Lei et al., 2017), L. gasseri OLL2809 (Itoh et al., 2011), and combined L. acidophilus, L. plantarum, L. fermentum and L. gasseri (Khodaverdi et al., 2019) reduces pain in people with knee osteoarthritis (Lei et al., 2017), and endometriosis (Itoh et al., 2011;Khodaverdi et al., 2019). Recently, faecal microbiota transplants have also been shown to reduce pain in those with fibromyalgia (Thurm et al., 2017) and Clostridium difficile infection (Alukal et al., 2019). Although these positive results could be due either to changes in the disease state or to changes in pain processing, they nonetheless suggest that exposure to greenspaceand their associated environmental microbiomesmay lead to reductions in pain, via changes in the human microbiome. ...
Article
Painful conditions are among the leading causes of years lived with disability. To reduce this burden, novel, cost-effective and accessible interventions are required. We propose that greenspace exposure may be one such intervention. Drawing on evidence from neuroscience, physiology, microbiology, and psychology, we articulate how and why exposure to greenspaces could improve pain outcomes and reduce the high global burden of pain. Greenspace exposure potentially provides opportunities to benefit from known or proposed health-enhancing components of nature, such as environmental microbiomes, phytoncides, negative air ions, sunlight, and the sights and sounds of nature itself. We review the established and potential links between these specific exposures and pain outcomes. While further research is required to determine possible causal links between greenspace exposure and pain outcomes, we suggest that there is already sufficient evidence to help reduce the global burden of pain by improving access and exposure to quality greenspaces.
... Those studies observed response rates of 41% (for 2 consecutive days of therapy) and 70% (2 consecutive days, and 2 additional days if needed) for chronic fatigue symptoms, and even higher response rates for GI symptoms, with benefits reported lasting up to 12-15 years in some cases. Similarly, a case-report [22] of six rounds of IMT resulted in "a total resolution of fatigue and depression." Results from these studies suggested that IMT can help with more than just gastrointestinal symptoms. ...
Article
Introduction: The purpose of this review is to discuss Microbiota Transplant Therapy (MTT), a type of intensive intestinal microbiota transplantation (IMT), for people with autism spectrum disorders (ASD) and chronic gastrointestinal disorders (constipation and/or diarrhea). Areas covered: This paper briefly reviews IMT, gastrointestinal symptoms and gastrointestinal bacteria in children with ASD, and results and lessons learned from intensive MTT for autism. Expert opinion: An open-label study and a two-year follow-up suggests that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.
Article
В статье проведен аналитический обзор литературы по теме влияния микробиоты человека на возникновение болевых синдромов различной этиологии и модальности. Исследования взаимоотношений по оси «микробиом – кишечник – головной мозг» показали их двунаправленный характер. Микроорганизмы кишечника регулируют обмен нейромедиаторов, работу иммунной системы, отношения по гипоталамо-гипофизарно-адреналовой оси. Основными путями, обеспечивающими взаимовлияния между микробиотой и организмом, являются волокна и образования вегетативной нервной системы, неокортекс. Влияние микробиоты на возникновение многих неврологических заболеваний и формирование болевого синдрома не вызывает сомнений и открывает перспективы разработки эффективных способов лечения. Приведены новые терапевтические стратегии лечения хронического болевого синдрома, основанные на современных знаниях о микробном разнообразии организма человека. The article presents an analytical review of the literature on the influence of the human microbiota on the occurrence of pain syndromes of various etiologies and modalities. Studies of the relationships along the microbiome – gut – brain axis have shown their bidirectional nature. Intestinal microorganisms regulate the exchange of neurotransmitters, the work of the immune system, and the relationship along the hypothalamic-pituitary-adrenal axis. The main pathways that provide interaction between the microbiota and the body are the fibers and formations of the autonomic nervous system, the neocortex. The influence of the microbiota on the occurrence of many neurological diseases and the formation of pain syndrome is beyond doubt and opens up prospects for the development of effective treatment methods. New therapeutic strategies for the treatment of chronic pain syndrome, based on modern knowledge about the microbial diversity of the human body, are presented.
Chapter
Chronic fatigue syndrome (CFS) is a combination of complex illness characterized by tiredness or intense fatigue that may worsen with too much exertion. Among the wide range of neuropsychological symptoms, 97% CFS patients have been reported with neuronal disorders such as headaches and symptoms in the emotional realm. Patients with CFS also show noticeable alterations in microflora, lowering level of Lactobacilli and Bifidobacterium. Recent researches explain that probiotics in the gastrointestinal tract (GIT) can greatly influence the neuronal pathways and central nervous system (CNS) to modulate behavior. Various studies expressed the benefit of probiotic therapy in normalizing fatigue patients and also restored mitochondrial electron transport function in patients with CFS. In this chapter, we provided a historical skeleton, bidirectional communication pathophysiology, selection criteria of probiotics, CFS treatment, and clinical implications of gut–brain connections. In summary, various aspects concerning the potential and safety of probiotics in the management of chronic fatigue syndrome are discussed in this chapter.
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Background We investigated whether the carriage of Blastocystis in IBS patients was associated with differences in the faecal microbiota. Forty patients with diarrhoea-predominant IBS (26 Blastocystis-positive and 14 Blastocystis-negative) and 57 healthy controls (HC) (42 Blastocystis-positive and 15 Blastocystis-negative) submitted faecal samples for metataxonomic analysis of the 16S ribosomal RNA gene. Differences in the relative abundance of bacteria in these IBS and HC groups were evaluated from phylum to genus level. ResultsSignificant changes were observed in two dominant phyla in IBS patients, regardless of Blastocystis infection status, namely a rise in Firmicutes and a statistically significant reduction in relative abundance of Bacteroidetes (with a threefold increase in the Firmicutes to Bacteoridetes ratio). Significant differences at genus level in IBS subjects compared to HC were also observed for many bacterial species. However, further clinical subgroup analysis of Blastocystis-positive and Blastocystis-negative subjects, regardless of symptoms, showed no significant differences at the phylum or genus level in IBS-P compared to IBS-N. Conclusions Significant differences in the faecal microbiota between diarrhoea-predominant IBS patients and healthy controls were confirmed, but the carriage of Blastocystis did not significantly alter the faecal microbiota. If Blastocystis-positive patients represent a separate clinical subtype of IBS, this group is not identified by changes in the microbiota.
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Background and aims: Few treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). A phase 3, randomized, double-blind, placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic rifaximin. Methods: The trial included adults with IBS-D, mean abdominal pain and bloating scores of 3 or more, and loose stool, located at 270 centers in the United States and Europe from February 2012 through June 2014. Those responding to a 2 week course of open-label rifaximin 550 mg 3 times daily who then relapsed during an observation phase (up to 18 weeks) were randomly assigned to groups given repeat treatments of rifaximin 550 mg or placebo, 3 times daily for 2 weeks. The primary endpoint was percentage of responders after first repeat treatment, defined as a decrease in abdominal pain of 30% or more from baseline and a decrease in frequency of loose stools of 50% or more from baseline, for 2 or more weeks during a 4-week posttreatment period. Results: Of 1074 patients (44.1%) who responded to open-label rifaximin, 382 (35.6%) did not relapse, whereas 692 (64.4%) did; of these, 636 were randomly assigned to receive repeat treatment with rifaximin (n=328) or placebo (n=308). The percentage of responders was significantly greater with rifaximin than placebo (38.1% vs 31.5%, P=.03). The percentage of responders for abdominal pain (50.6% vs 42.2%, P=.018) was significantly greater with rifaximin than placebo, but not stool consistency (51.8% vs 50.0%, P=.42). Significant improvements were also noted for prevention of recurrence, durable response, and bowel movement urgency. Adverse event rates were low and similar between groups. Conclusions: In a phase 3 study of patients with relapsing symptoms of IBS-D, repeat rifaximin treatment was efficacious and well tolerated.
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Objective The original European League Against Rheumatism recommendations for managing fibromyalgia assessed evidence up to 2005. The paucity of studies meant that most recommendations were ‘expert opinion’. Methods A multidisciplinary group from 12 countries assessed evidence with a focus on systematic reviews and meta-analyses concerned with pharmacological/non-pharmacological management for fibromyalgia. A review, in May 2015, identified eligible publications and key outcomes assessed were pain, fatigue, sleep and daily functioning. The Grading of Recommendations Assessment, Development and Evaluation system was used for making recommendations. Results 2979 titles were identified: from these 275 full papers were selected for review and 107 reviews (and/or meta-analyses) evaluated as eligible. Based on meta-analyses, the only ‘strong for’ therapy-based recommendation in the guidelines was exercise. Based on expert opinion, a graduated approach, the following four main stages are suggested underpinned by shared decision-making with patients. Initial management should involve patient education and focus on non-pharmacological therapies. In case of non-response, further therapies (all of which were evaluated as ‘weak for’ based on meta-analyses) should be tailored to the specific needs of the individual and may involve psychological therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance) and/or a multimodal rehabilitation programme (for severe disability). Conclusions These recommendations are underpinned by high-quality reviews and meta-analyses. The size of effect for most treatments is relatively modest. We propose research priorities clarifying who will benefit from specific interventions, their effect in combination and organisation of healthcare systems to optimise outcome.
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Article
Background: Gastrointestinal disturbances are among symptoms commonly reported by individuals diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, whether ME/CFS is associated with an altered microbiome has remained uncertain. Here, we profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from stool as well as inflammatory markers from serum for cases (n = 48) and controls (n = 39). We also examined a set of inflammatory markers in blood: C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14). Results: We observed elevated levels of some blood markers for microbial translocation in ME/CFS patients; levels of LPS, LBP, and sCD14 were elevated in ME/CFS subjects. Levels of LBP correlated with LPS and sCD14 and LPS levels correlated with sCD14. Through deep sequencing of bacterial rRNA markers, we identified differences between the gut microbiomes of healthy individuals and patients with ME/CFS. We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum. In the patient cohort, we find less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory. Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as ME/CFS with a cross-validation accuracy of 82.93 %. Conclusions: Our results indicate dysbiosis of the gut microbiota in this disease and further suggest an increased incidence of microbial translocation, which may play a role in inflammatory symptoms in ME/CFS.
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Article
Background Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases, affecting 11.2 % of people worldwide. Previous studies have shown that probiotic treatment may benefit IBS patients. However, the effect of probiotics and the appropriate type, dose, and treatment duration for IBS are still unclear. The aim of the current study was to assess the efficacy of different probiotic types, doses and treatment durations in IBS patients diagnosed by Rome III criteria via a meta-analysis of randomized controlled trials (RCTs). Methods Medline, EMBASE, and the Cochrane Central Register of Controlled Trials up to October 2015 were searched. RCTs including comparisons between the effects of probiotics and placebo on IBS patients diagnosed by Rome III criteria were eligible. Dichotomous data were pooled to obtain the relative risk (RR) with a 95 % confidence interval (CI), whereas continuous data were pooled using a standardized mean difference (SMD) with a 95 % CI. ResultsTwenty-one RCTs were included in this meta-analysis. Probiotic therapy was associated with more improvement than placebo administration in overall symptom response (RR: 1.82, 95 % CI 1.27 to 2.60) and quality of life (QoL) (SMD: 0.29, 95 % CI 0.08 to 0.50), but not in individual IBS symptoms. Single probiotics, a low dose, and a short treatment duration were more effective with respect to overall symptom response and QoL. No differences were detected in individual IBS symptoms in the subgroup analyses. Conclusion Probiotics are an effective pharmacological therapy in IBS patients. Single probiotics at a low dose and with a short treatment duration appear to be more effective in improving overall symptom response and QoL, but more evidence for these effects is still needed.
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Article
Fecal microbiota transplantation (FMT) is the infusion of liquid filtrate feces from a healthy donor into the gut of a recipient to cure a specific disease. A fecal suspension can be administered by nasogastric or nasoduodenal tube, colonoscope, enema, or capsule. The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated FMT as an emerging treatment for a wide range of disorders, including Parkinson's disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism. There are many unanswered questions regarding FMT, including donor selection and screening, standardized protocols, long-term safety, and regulatory issues. This article reviews the efficacy and safety of FMT used in treating a variety of diseases, methodology, criteria for donor selection and screening, and various concerns regarding FMT.
Article
Background: Chronic fatigue syndrome is a widespread condition with a huge impact not only on a patient's life, but also on society as evidenced by substantial losses of productivity, informal costs, and medical expenses. The high prevalence rates (0.2-6.4%) and the low employment rates (27-41%) are responsible for the enormous burden imposed on society, with loss of productivity representing the highest cost. The objective of this review is to systematically review the recent literature on chronic fatigue syndrome/myalgic encephalomyelitis. Methods: The published literature between 1 January 1990 and 1 April 2015 was searched using the MEDLINE, Cochrane Library, and Web of Sciences databases. The reference lists of the selected articles were screened for other relevant articles. Results and conclusions: Despite extensive research, none of the proposed etiological factors have shown strong, reproducible scientific evidence. Over the years, the biopsychosocial model integrating many of the proposed hypotheses has been gaining popularity over the biomedical model, where the focus is on one physical cause. Since the etiological mechanism underlying chronic fatigue syndrome is currently unknown, disease-specific treatments do not exist. Various treatments have been investigated but only cognitive behavior therapy (CBT) and graded exercise therapy (GET) have shown moderate effectiveness.
Article
Functional bowel disorders are highly prevalent disorders found worldwide. These disorders have the potential to affect all members of society, regardless of age, gender, race, creed, color or socioeconomic status. Improving our understanding of functional bowel disorders (FBD) is critical as they impose a negative economic impact to the global health care system in addition to reducing quality of life. Research in the basic and clinical sciences during the past decade has produced new information on the epidemiology, etiology, pathophysiology, diagnosis and treatment of FBDs. These important findings created a need to revise the Rome III criteria for FBDs, last published in 2006. This manuscript classifies the FBDs into five distinct categories: irritable bowel syndrome (IBS); functional constipation (FC); functional diarrhea (FDr); functional abdominal bloating/distention (FAB/D); and unspecified FBD (U-FBD). Also included in this article is a new sixth category, opioid induced constipation (OIC) which is distinct from the functional bowel disorders (FBDs). Each disorder will first be defined, followed by sections on epidemiology, rationale for changes from prior criteria, clinical evaluation, physiologic features, psychosocial features and treatment. It is the hope of this committee that this new information will assist both clinicians and researchers in the decade to come.
Article
Fibromyalgia syndrome (FMS) is a clinical disorder predominant in females with unknown etiology and medically unexplained symptoms (MUS), similar to other afflictions, including irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD), Gulf War illness (GFI), and others. External environmental stimuli drive behavior and impact physiologic homeostasis (internal environment) via autonomic functioning. These environments directly impact the individual affective state (mind), which feeds back to regulate physiology (body). FMS has emerged as a complex disorder with pathologies identified among neurotransmitter and enzyme levels, immune/cytokine functionality, cortical volumes, cutaneous innervation, as well as an increased frequency among people with a history of traumatic and/or emotionally negative events, and specific personality trait profiles. Yet, quantitative physical evidence of pathology or disease etiology among FMS has been limited (as with other afflictions with MUS). Previously, our group published findings of increased peptidergic sensory innervation associated with the arterio-venous shunts (AVS) in the glabrous hand skin of FMS patients, which provides a plausible mechanism for the wide-spread FMS symptomology. This review focuses on FMS as a model affliction with MUS to discuss the implications of the recently discovered peripheral innervation alterations, explore the role of peripheral innervation to central sensitization syndromes (CSS), and examine possible estrogen-related mechanisms through which external and internal environmental factors may contribute to FMS etiology and possibly other afflictions with MUS.