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Many men with chronic pelvic pain report symptoms of CFS, IBS & Fibromyalgia. Is there a connection?
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Jun 29, 2017, 10:49:21 AM6/29/17
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Many men with chronic pelvic pain report symptoms of CFS, IBS and Fibromyalgia. Is there a connection?
Note: CFS = Chronic Fatigue Syndrome, IBS = Irritable Bowel Syndrome, Fibro = Fibromyalgia.
Many Patients have reported a CFS-like illness at or near the onset of their CP/CPPS. Recent studies have shown that CFS is indeed linked to chronic prostatitis. In general, studies have found that there is an association between urologic chronic pelvic pain syndromes (CPPS and IC) with conditions like chronic fatigue, fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, and temporomandibular disorder.
Chronic Fatigue Syndrome
Chronic Fatigue Syndrome (CFS), also sometimes called myalgic encephalomyelitis (ME) in Europe, is defined as unexplained chronic fatigue that lasts for more than six months, impairs normal activities and has no identifiable medical or psychological problems to account for it.
Four or more of the following symptoms must have been present for longer than six months:
short-term memory loss or a severe inability to concentrate that affects work, school, or other normal activities
sore throat
swollen lymph nodes (eg. in the neck or armpits)
muscle pain
pain without redness or swelling in a number of joints
intense or changing patterns of headaches
unrefreshing sleep
after any exertion, weariness that lasts for more than a day
The fatigue must be severe: sleep or rest does not relieve it; the fatigue is not the result of excessive work or exercise; the fatigue substantially impairs a person’s ability to function normally at home, at work, and in social occasions. Even mild exercise often makes the symptoms, especially fatigue, much worse.
Irritable Bowel Syndrome
Symptoms of irritable bowel syndrome (IBS) include abdominal pain, mucus in the stools, and alternating diarrhoea and constipation. Other terms for irritable bowel syndrome include ‘spastic colon’ and ‘irritable colon’. Some of the more common signs of irritable bowel syndrome include:
Abdominal pain or cramping that is often relieved by passing wind or faeces
Alternating diarrhoea and constipation
A sensation that the bowels are not fully emptied after passing a motion
Abdominal bloating
Mucus present in the stools
Nausea
Irritable bowel syndrome can be subdivided into three major categories:
Constipation-predominant – the person tends to alternate constipation with normal stools. Symptoms of abdominal cramping or aching are commonly triggered by eating.
Diarrhoea-predominant – the person tends to experience diarrhoea first thing in the morning or after eating. The need to go to the toilet is typically urgent and cannot be delayed. Incontinence may be a problem.
Alternating constipation and diarrhoea.
Note: recent studies have shown a link between IBS and certain sugars, and it is possible to cure yourself of IBS following a special diet.
Fibromyalgia
Fibromyalgia is a condition in which people describe symptoms that include widespread pain and tenderness in the body, often accompanied by fatigue, cognitive disturbance and emotional distress. The most common symptoms are:
increased sensitivity to pain due to a decreased pain threshold
increased responsiveness to sensory stimuli such as heat, cold, light and numbness or tingling
extreme fatigue (tiredness)
problems with cognition (impacting on memory and concentration)
problems with sleep
Symptoms can be mild, moderate or severe. Symptoms may disappear for extended periods of time, perhaps even years. Some people with fibromyalgia have other symptoms, such as irritable bowel syndrome, irritable or overactive bladder, headaches, and swelling and numbness or tingling in the arms and legs. Living with ongoing pain and fatigue often leads to secondary problems such as anxiety and depression.
Symptoms similar in CFS, temporomandibular disorder and fibromyalgia
By Elda Hauschildt
CHICAGO: There is now preliminary evidence that patients with chronic fatigue syndrome, fibromyalgia and temporomandibular disorder share the same key symptoms.
These symptoms include generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. Researchers also say it is apparent that seven other localized and systemic illnesses may occur at the same time as the three conditions.
These include chronic tension-type headache, irritable bowel syndrome, bladder pain syndrome/interstitial cystitis (BPS/IC), post-concussive syndrome, multiple chemical sensitivities, chronic pelvic pain and chronic low back pain.
Seattle researchers recruited 25 chronic fatigue patients, 22 fibromyalgia patients and 25 temporomandibular patients from hospital- based clinics. All of the patients were diagnosed by their physicians. The control group numbered 22 healthy subjects from a dermatology clinic.
All participants completed a 138-item symptom checklist. They then underwent brief physical examinations.
Most patients reported few past diagnoses of the 10 clinical conditions outside of their primary diagnosis. Patients diagnosed with each of the three main conditions were more likely than control subjects to meet lifetime symptom and diagnostic criteria for many of the other conditions.
The most striking finding was that of lifetime rates of irritable bowel syndrome. Researchers found the syndrome in 92 per cent of chronic fatigue, 77 per cent of fibromyalgia, and 64 per cent of temporomandibular disorder patients.
Archives of Internal Medicine, 2000; 160: 221-227
http://www.chronicprostatitis.com/chronic-prostatitis-linked-to-cfs-ibs-and-fibro/
*****
Science, Art, Beauty by Josiah Zayner, Ph.D.
JUL
5
I transplanted someone else's microbiome in(on)to my body and it was so surreal - Results - Part III
This is a case study of a 35 year old caucasian Male of European ancestry living in the United States, a maternal Haplogroup of H1e1a and a paternal haplogroup of I1*. NOD2 Genotype SNP(rs2066844) CC indicating decreased risk of Crohn’s disease. The subject presented with increased bowel movements(3+ times a day) Bristol type stool 5-7, mainly 6. Blood in stool more than 2 but less than 5 times a month. Experiences nausea, abdominal cramps and pain 2 or more days a week with no correlated inducers besides stress. Diet consists mainly of rice, vegetables and meat protein(chicken or pork). Eats out 1-2 times per week. Average kilocalories consumed per day ~2100. Height 5’9”(1.75 m) weight before experiment 167 lbs (76 kg). Exercises 1-2 days per week. Subject also presents with type II bipolar disorder and takes clonazepam as needed to help sleep. Subject has chronic sinusitis with no clear cause and has been tested for allergies and nasal polyps both coming back negative or inconclusive. Subject has been diagnosed with chronic prostatitis and was treated with ciprofloxacin and then bactrim in Dec. 2013(also last time antibiotics were taken) which did not relieve symptoms. Acute symptoms resolved to mild pain during urination.
The subject attempted a full body microbial transplant from a healthy donor Male caucasian ~30 year of age using fresh stool samples, skin, mouth and nasal swabs. Bacterial swabs were taken from, skin, mouth, nose, poop and environment before and throughout the experiment using sterile swabs and stored in 150mM NaCl and 0.01% Tween.
The subject self treated with 500 mg Tetracycline and 500 mg Ciprofloxacin, four doses over 2.5 days. Subject also performed a complete body scrub with soap and tetracycline, including a nasal rinse. The subject proceeded to stay in a precleaned hotel room using new untouched sheets. The subject did not touch another person during the course of the transplant without the use of nitrile gloves. The subject stayed in the hotel room for 3 days and 3 nights during which he ingest 3-6 grams of donor feces enclosed in gelatin pills. He coated himself with 20-50mL saline solution containing swabs from the donors skin. He also inoculated his mouth and nasal passages no less than 6 times with the donors swabs. Patient returned home and attempted to clean and sterilize ~700 sq ft (65 sq m) apartment and inoculate it with donor skin bacterial cultures.
Within one week of the experiment the subject’s bowel movements were consistently reduced to 1 time per day. Stomach pains and cramps reduced almost completely within 2 weeks. Subjects weight reduce to an average of ~ 160 lbs(73 kg) 2 months after the experiment. Diet has remained very similar(rice, veg, meat) except subject notices more meat(no craving) and a newfound craving for sugary foods. Prostatitis resolved completely. Symptoms from post nasal drip seem reduced but uncertain, symptoms still flare up at least 2-5 times a month. Bipolar disorder not affected.
A total of 77 samples were collected before, during and after experiment. DNA extraction, 16s amplicon library prep using 515f and 806r and Illumina MiSeq 151x151 sequencing was done by Argonne National Lab in Batavia Illinois. Of the 77 samples 73 had counts.
Data Analysis
QIIME 1.9.1 was used for data analysis
Samples 65(storage buffer) and 66(storage buffer and sterile swab) were control samples and used to filter out contamination using standard QIIME workflow. Afterward sample #55 had below 1000 counts and so was removed from the rest of the study.
Beta diversity was calculated for poop samples using a jacknifed subset of 5000 sequences. PCoA plots of weighted UniFrac are displayed below.
poopPCoA.labeled.png
Less than two weeks after the transplant the microbiota in the gut of the subject became more closely related to the donors gut microbiota than to the subjects gut microbiota before the experiment.
Observing the different types of bacteria in the samples both on the Class and Family levels, the subjects gut had increased diversity before the transplant (#9 and #11) as compared to after the transplant (50, 51, 52, 53) and had more similar diversity to the donor’s samples (59, 60). Diversity was insinuated by the portion of a sample belonging to species other than those the top 10-15 samples, Shown by "Other".
Posted 5th July by Josiah Zayner
http://www.ifyoudontknownowyaknow.com/2016/07/i-transplanted-someone-elses-microbiome.html?m=1
*****
Analysis of Gut Microbiome Reveals Significant Differences between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls.
Urol. 2016 Aug;196(2):435-41. doi: 10.1016/j.juro.2016.02.2959. Epub 2016 Feb 27.
Analysis of Gut Microbiome Reveals Significant Differences between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls.
Shoskes DA1, Wang H2, Polackwich AS3, Tucky B3, Altemus J4, Eng C5.
Author information
Abstract
PURPOSE:
Chronic prostatitis/chronic pelvic pain syndrome is a common disorder with heterogeneous etiologies and clinical features. The gut microbiome is a metabolically active ecosystem linked to systemic conditions (gut-brain axis). We hypothesize that the gut microbiome will show alterations between patients with chronic pelvic pain syndrome and controls.
MATERIALS AND METHODS:
We identified patients with chronic pelvic pain syndrome and controls who were asymptomatic or only had urinary tract symptoms. After rectal examination the soiled glove tip was immersed in sterile saline and stored on ice. Symptom severity was measured with the NIH-Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the pellet of samples. MiSeq sequencing of bacterial specific 16S rRNA capture was performed. Taxonomic and bioinformatic analyses were performed using principal coordinate analysis, QIIME and LEfSe algorithms.
RESULTS:
There were 25 patients and 25 controls with complete data. Mean age was similar (chronic pelvic pain syndrome 52.3 vs control 57.0 years, p=0.27). For patients with chronic pelvic pain syndrome median symptom duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0 and mean UPOINT domain was 3.6. Three-dimensional UniFrac principal coordinate analysis revealed tighter clustering of controls in a space distinct from the wider clustering of cases (p=0.001) with cases having decreased alpha diversity (p=0.001). Compared to controls, 3 taxa were overrepresented in cases and 12 were underrepresented, eg Prevotella.
CONCLUSIONS:
Patients with chronic pelvic pain syndrome have significantly less gut microbiome diversity which clusters differently from controls, and robustly lower counts of Prevotella, with separation sufficient to serve as a potential biomarker. The gut microbiome may serve as disease biomarker and potential therapeutic target in chronic pelvic pain syndrome.
Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
gastrointestinal microbiome; pelvic pain; prostatitis
PMID: 26930255 DOI: 10.1016/j.juro.2016.02.2959
[PubMed - in process]
https://www.ncbi.nlm.nih.gov/pubmed/26930255
*****
Microbiomes of Pelvic Pain - ClinicalTrials.gov
https://clinicaltrials.gov/ct2/show/study/NCT01738464
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Microbiomes of Pelvic Pain
This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Northwestern University
Sponsor:
Northwestern University
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
David Klumpp, Northwestern University
ClinicalTrials.gov Identifier:
NCT01738464
First received: November 28, 2012
Last updated: April 6, 2016
Last verified: April 2016
History of Changes
Full Text View Tabular ViewNo Study Results PostedDisclaimerHow to Read a Study Record
Purpose
This research study seeks to provide more insight as to how the microbiome affects or is affected by conditions causing chronic pelvic pain such as Interstitial Cystitis (IC), Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Symptoms (LUTS), or Overactive bladder (OAB). Depression and many chronic pain disorders are often related and are poorly understood, and treatment is often not helpful. The goal of this study is to explain pelvic pain characteristics and causes by studying microbiomes of healthy people compared to people suffering from IC, CP/CPPS, LUTS, OAB, and Major depression.
Condition
Interstitial Cystitis
Chronic Prostatitis
Chronic Pelvic Pain Syndrome
Lower Urinary Tract Symptoms
Overactive Bladder
Major Depression
Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Microbiomes of Pelvic Pain
Resource links provided by NLM:
MedlinePlus related topics: Interstitial Cystitis Pelvic Pain Urine and Urination
U.S. FDA Resources
Further study details as provided by Northwestern University:
Primary Outcome Measures:
Genotype Anaerobic Bacterial populations between Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and Major Depression [ Time Frame: 1 day ] [ Designated as safety issue: No ]
Anaerobic bacteria will be collected from a fecal specimen from both Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and/or Major Depression. Genotyping will be done to differentiate bacterial populations between the Control patients and patients with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and/or Major Depression.
Biospecimen Retention: Samples With DNA
Stool specimen
Estimated Enrollment: 300
Study Start Date: June 2012
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pelvic Pain
Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, and Overactive Bladder patients will be compared to Healthy patients.
Controls
Healthy patients will be used as controls to compare to patients diagnosed with interstitial cystitis, chronic prostatitis, chronic pelvic pain syndrome, Lower Urinary Tract Symptoms, or Overactive Bladder
Major Depression
Major Depressed patients will be compared to Controls and Pelvic Pain cohorts.
Detailed Description:
Interstitial cystitis/painful bladder syndrome (IC), Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Infection Symptoms (LUTS), and Overactive bladder (OAB) are characterized by chronic pelvic pain and voiding dysfunction.These conditions remain an enigma within urology, with no known etiology or widely effective therapies. However, some IC/CP/CPPS/LUTS/OAB and depressed patients suffer bowel co-morbidities, and it is well established that the GI tract can influence bladder function, mood, and sensation via pelvic organ crosstalk. Like other body sites, the gut harbors a rich microflora. It is also well established that IC/CP/CPPS/LUTS/OAB patients often suffer from depression. Therefore, in addition to IC/CP/CPPS/LUTS/OAB patients, we seek patients currently suffering from major depression. Our goal is to identify differences in gut microbiota associated with pelvic pain and determine the mechanisms by which gut microbiota influence gut-brain interactions in pelvic pain. Studies characterizing microbial diversity and relative abundance at a particular body site, the "microbiome," reveal that microbiomes play critical roles in normal cellular and organ function, and thus this importance is emphasized with the Human Microbiome Project (HMP), an NIH Common Fund initiative. Microbiomes are also dynamic and subject to skewing, and these changes are increasingly associated with diseases including Crohn's disease, ulcerative colitis, obesity, and possibly depression. Antibiotic therapies alter microbiomes, often causing temporary dysfunction and sometimes resulting in diseases such as colitis. Since IC/CP/CPPS/LUTS/OAB patients often have a history of urinary tract infection (UTI), they typically receive multiple courses of antibiotics. This therapeutic history of IC/CP/CPPS/LUTS/OAB patients may have adverse consequences for two reasons. First, potential skewing of the gut microbiome may alter normal sensory and functional homeostatic mechanisms, contributing to pain and voiding dysfunction. Second, an altered gut microbiome may foster uropathogen reservoir expansion, and our preliminary data demonstrate urinary E. coli isolates can induce chronic pelvic pain persisting long after microbial clearance. Together these lines of reasoning raise the provocative possibility that microbiomes contribute to IC/CP/CPPS/LUTS/OAB and depression directly by supplying uropathogens or indirectly through organ crosstalk dysfunction. Therefore, is an altered gastrointestinal and/or reproductive tract microbiome associated with these chronic pelvic pain conditions and depression? Our team marries core NIH and NIDDK missions, digestive diseases and kidney/urologic as well psychiatric disciplines, to address this novel question with synergistic expertise in clinical diagnosis of IC/CP/CPPS/LUTS/OAB and depression, quantifying GI tract microbiomes, and neural mechanisms of microbe-induced pelvic pain or depression.
Eligibility
Ages Eligible for Study: 18 Years to 60 Years (Adult)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Sampling Method: Non-Probability Sample
Study Population
Primary care clinic patients Community sample
Criteria
Inclusion Criteria:
Any sex
Between the ages of 18 and 60
Any ethnicity
Have provided informed consent
Physician diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), interstitial cystitis/painful bladder syndrome (IC/PBS), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), Lower Urinary Tract Symptoms, Overactive Bladder, or Major Depression.
Report symptoms of discomfort or pain in the pelvic or abdominal region of moderate severity for at least a three (3) month period within the last six (6) months, who have been currently diagnosed with major depression
Are healthy, age matched, controls.
Exclusion Criteria:
For IC/CPPS/LUTS/OAB
Evidence of facultative Gram negative or enterococcus with a value of ≥ 100,000 colony forming units (CFU)/milliliter in mid-stream urine (VB2)
Secondary chronic pain condition which would prevent a clear interpretation of the study results
A history of tuberculous cystitis, bladder cancer, carcinoma in situ, or urethral cancer; history of alcohol abuse, inflammatory bowel disease, pelvic radiation or systemic chemotherapy, intravesical chemotherapy, intravesical Bacillus Calmette-Guerin (BCG), active urethral stricture, ureteral calculi, urethral diverticulum, or neurological disease or disorder affecting the bladder or gut
Unlikely to be compliant due to unmanaged medical or psychological conditions, including neurological, psychological or speech/language problems that will interfere or prevent with their understanding of consent
Ability to comply with the protocol or ability to complete the study
Pregnant or Syndromes of Chronic Pelvic Pain (SCPP) symptoms are present only during menses
And if there was antibiotic use in the last 6 months
For Depressed Patients:
Participant is in remission or has recovered from major depression, has substance abuse in the past 6 months, has been diagnosed with any bipolar or psychotic disorder, has been diagnosed with any severe cognitive impairment or dementia, history of cancer (with the exception of skin cancer), has current major psychiatric disorder or other psychiatric or medical comorbidities that would interfere with study participation (e.g. dementia, psychosis, upcoming major surgery, lupus, active heart failure, diabetes, etc., currently has a UTI and/or has had a positive urine culture in the past 6 weeks, and if there was antibiotic use in the last 3 months.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738464
Contacts
Contact: David J Klumpp, PhD 312.908.1996 d-kl...@northwestern.edu
Contact: Anthony J Schaeffer, MD 312.908.9844 ajsch...@northwestern.edu
Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: David J Klumpp, PhD Northwestern University
More Information
Responsible Party: David Klumpp, Associate Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT01738464 History of Changes
Other Study ID Numbers: STU00055668 1R24DK094575-01
Study First Received: November 28, 2012
Last Updated: April 6, 2016
Health Authority: United States: Institutional Review Board
Keywords provided by Northwestern University:
Pelvic Pain
Interstitial Cystitis
Microbiome
Prostatitis
Chronic
Depression
Additional relevant MeSH terms:
Depression
Urinary Bladder, Overactive
Depressive Disorder, Major
Lower Urinary Tract Symptoms
Cystitis, Interstitial
Pelvic Pain
Cystitis
Prostatitis
Behavioral Symptoms
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Pain
Neurologic Manifestations
Prostatic Diseases
Genital Diseases, Male
ClinicalTrials.gov processed this record on December 15, 2016
Copyright Privacy Accessibility Viewers and Players Freedom of Information Act USA.gov
U.S. National Library of Medicine U.S. National Institutes of Health U.S. Department of Health and Human Services
https://clinicaltrials.gov/ct2/show/study/NCT01738464
Note: CFS = Chronic Fatigue Syndrome, IBS = Irritable Bowel Syndrome, Fibro = Fibromyalgia.
Many Patients have reported a CFS-like illness at or near the onset of their CP/CPPS. Recent studies have shown that CFS is indeed linked to chronic prostatitis. In general, studies have found that there is an association between urologic chronic pelvic pain syndromes (CPPS and IC) with conditions like chronic fatigue, fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, and temporomandibular disorder.
Chronic Fatigue Syndrome
Chronic Fatigue Syndrome (CFS), also sometimes called myalgic encephalomyelitis (ME) in Europe, is defined as unexplained chronic fatigue that lasts for more than six months, impairs normal activities and has no identifiable medical or psychological problems to account for it.
Four or more of the following symptoms must have been present for longer than six months:
short-term memory loss or a severe inability to concentrate that affects work, school, or other normal activities
sore throat
swollen lymph nodes (eg. in the neck or armpits)
muscle pain
pain without redness or swelling in a number of joints
intense or changing patterns of headaches
unrefreshing sleep
after any exertion, weariness that lasts for more than a day
The fatigue must be severe: sleep or rest does not relieve it; the fatigue is not the result of excessive work or exercise; the fatigue substantially impairs a person’s ability to function normally at home, at work, and in social occasions. Even mild exercise often makes the symptoms, especially fatigue, much worse.
Irritable Bowel Syndrome
Symptoms of irritable bowel syndrome (IBS) include abdominal pain, mucus in the stools, and alternating diarrhoea and constipation. Other terms for irritable bowel syndrome include ‘spastic colon’ and ‘irritable colon’. Some of the more common signs of irritable bowel syndrome include:
Abdominal pain or cramping that is often relieved by passing wind or faeces
Alternating diarrhoea and constipation
A sensation that the bowels are not fully emptied after passing a motion
Abdominal bloating
Mucus present in the stools
Nausea
Irritable bowel syndrome can be subdivided into three major categories:
Constipation-predominant – the person tends to alternate constipation with normal stools. Symptoms of abdominal cramping or aching are commonly triggered by eating.
Diarrhoea-predominant – the person tends to experience diarrhoea first thing in the morning or after eating. The need to go to the toilet is typically urgent and cannot be delayed. Incontinence may be a problem.
Alternating constipation and diarrhoea.
Note: recent studies have shown a link between IBS and certain sugars, and it is possible to cure yourself of IBS following a special diet.
Fibromyalgia
Fibromyalgia is a condition in which people describe symptoms that include widespread pain and tenderness in the body, often accompanied by fatigue, cognitive disturbance and emotional distress. The most common symptoms are:
increased sensitivity to pain due to a decreased pain threshold
increased responsiveness to sensory stimuli such as heat, cold, light and numbness or tingling
extreme fatigue (tiredness)
problems with cognition (impacting on memory and concentration)
problems with sleep
Symptoms can be mild, moderate or severe. Symptoms may disappear for extended periods of time, perhaps even years. Some people with fibromyalgia have other symptoms, such as irritable bowel syndrome, irritable or overactive bladder, headaches, and swelling and numbness or tingling in the arms and legs. Living with ongoing pain and fatigue often leads to secondary problems such as anxiety and depression.
Symptoms similar in CFS, temporomandibular disorder and fibromyalgia
By Elda Hauschildt
CHICAGO: There is now preliminary evidence that patients with chronic fatigue syndrome, fibromyalgia and temporomandibular disorder share the same key symptoms.
These symptoms include generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. Researchers also say it is apparent that seven other localized and systemic illnesses may occur at the same time as the three conditions.
These include chronic tension-type headache, irritable bowel syndrome, bladder pain syndrome/interstitial cystitis (BPS/IC), post-concussive syndrome, multiple chemical sensitivities, chronic pelvic pain and chronic low back pain.
Seattle researchers recruited 25 chronic fatigue patients, 22 fibromyalgia patients and 25 temporomandibular patients from hospital- based clinics. All of the patients were diagnosed by their physicians. The control group numbered 22 healthy subjects from a dermatology clinic.
All participants completed a 138-item symptom checklist. They then underwent brief physical examinations.
Most patients reported few past diagnoses of the 10 clinical conditions outside of their primary diagnosis. Patients diagnosed with each of the three main conditions were more likely than control subjects to meet lifetime symptom and diagnostic criteria for many of the other conditions.
The most striking finding was that of lifetime rates of irritable bowel syndrome. Researchers found the syndrome in 92 per cent of chronic fatigue, 77 per cent of fibromyalgia, and 64 per cent of temporomandibular disorder patients.
Archives of Internal Medicine, 2000; 160: 221-227
http://www.chronicprostatitis.com/chronic-prostatitis-linked-to-cfs-ibs-and-fibro/
*****
Science, Art, Beauty by Josiah Zayner, Ph.D.
JUL
5
I transplanted someone else's microbiome in(on)to my body and it was so surreal - Results - Part III
This is a case study of a 35 year old caucasian Male of European ancestry living in the United States, a maternal Haplogroup of H1e1a and a paternal haplogroup of I1*. NOD2 Genotype SNP(rs2066844) CC indicating decreased risk of Crohn’s disease. The subject presented with increased bowel movements(3+ times a day) Bristol type stool 5-7, mainly 6. Blood in stool more than 2 but less than 5 times a month. Experiences nausea, abdominal cramps and pain 2 or more days a week with no correlated inducers besides stress. Diet consists mainly of rice, vegetables and meat protein(chicken or pork). Eats out 1-2 times per week. Average kilocalories consumed per day ~2100. Height 5’9”(1.75 m) weight before experiment 167 lbs (76 kg). Exercises 1-2 days per week. Subject also presents with type II bipolar disorder and takes clonazepam as needed to help sleep. Subject has chronic sinusitis with no clear cause and has been tested for allergies and nasal polyps both coming back negative or inconclusive. Subject has been diagnosed with chronic prostatitis and was treated with ciprofloxacin and then bactrim in Dec. 2013(also last time antibiotics were taken) which did not relieve symptoms. Acute symptoms resolved to mild pain during urination.
The subject attempted a full body microbial transplant from a healthy donor Male caucasian ~30 year of age using fresh stool samples, skin, mouth and nasal swabs. Bacterial swabs were taken from, skin, mouth, nose, poop and environment before and throughout the experiment using sterile swabs and stored in 150mM NaCl and 0.01% Tween.
The subject self treated with 500 mg Tetracycline and 500 mg Ciprofloxacin, four doses over 2.5 days. Subject also performed a complete body scrub with soap and tetracycline, including a nasal rinse. The subject proceeded to stay in a precleaned hotel room using new untouched sheets. The subject did not touch another person during the course of the transplant without the use of nitrile gloves. The subject stayed in the hotel room for 3 days and 3 nights during which he ingest 3-6 grams of donor feces enclosed in gelatin pills. He coated himself with 20-50mL saline solution containing swabs from the donors skin. He also inoculated his mouth and nasal passages no less than 6 times with the donors swabs. Patient returned home and attempted to clean and sterilize ~700 sq ft (65 sq m) apartment and inoculate it with donor skin bacterial cultures.
Within one week of the experiment the subject’s bowel movements were consistently reduced to 1 time per day. Stomach pains and cramps reduced almost completely within 2 weeks. Subjects weight reduce to an average of ~ 160 lbs(73 kg) 2 months after the experiment. Diet has remained very similar(rice, veg, meat) except subject notices more meat(no craving) and a newfound craving for sugary foods. Prostatitis resolved completely. Symptoms from post nasal drip seem reduced but uncertain, symptoms still flare up at least 2-5 times a month. Bipolar disorder not affected.
A total of 77 samples were collected before, during and after experiment. DNA extraction, 16s amplicon library prep using 515f and 806r and Illumina MiSeq 151x151 sequencing was done by Argonne National Lab in Batavia Illinois. Of the 77 samples 73 had counts.
Data Analysis
QIIME 1.9.1 was used for data analysis
Samples 65(storage buffer) and 66(storage buffer and sterile swab) were control samples and used to filter out contamination using standard QIIME workflow. Afterward sample #55 had below 1000 counts and so was removed from the rest of the study.
Beta diversity was calculated for poop samples using a jacknifed subset of 5000 sequences. PCoA plots of weighted UniFrac are displayed below.
poopPCoA.labeled.png
Less than two weeks after the transplant the microbiota in the gut of the subject became more closely related to the donors gut microbiota than to the subjects gut microbiota before the experiment.
Observing the different types of bacteria in the samples both on the Class and Family levels, the subjects gut had increased diversity before the transplant (#9 and #11) as compared to after the transplant (50, 51, 52, 53) and had more similar diversity to the donor’s samples (59, 60). Diversity was insinuated by the portion of a sample belonging to species other than those the top 10-15 samples, Shown by "Other".
Posted 5th July by Josiah Zayner
http://www.ifyoudontknownowyaknow.com/2016/07/i-transplanted-someone-elses-microbiome.html?m=1
*****
Analysis of Gut Microbiome Reveals Significant Differences between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls.
Urol. 2016 Aug;196(2):435-41. doi: 10.1016/j.juro.2016.02.2959. Epub 2016 Feb 27.
Analysis of Gut Microbiome Reveals Significant Differences between Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Controls.
Shoskes DA1, Wang H2, Polackwich AS3, Tucky B3, Altemus J4, Eng C5.
Author information
Abstract
PURPOSE:
Chronic prostatitis/chronic pelvic pain syndrome is a common disorder with heterogeneous etiologies and clinical features. The gut microbiome is a metabolically active ecosystem linked to systemic conditions (gut-brain axis). We hypothesize that the gut microbiome will show alterations between patients with chronic pelvic pain syndrome and controls.
MATERIALS AND METHODS:
We identified patients with chronic pelvic pain syndrome and controls who were asymptomatic or only had urinary tract symptoms. After rectal examination the soiled glove tip was immersed in sterile saline and stored on ice. Symptom severity was measured with the NIH-Chronic Prostatitis Symptom Index and clinical phenotype with UPOINT. Total DNA was extracted from the pellet of samples. MiSeq sequencing of bacterial specific 16S rRNA capture was performed. Taxonomic and bioinformatic analyses were performed using principal coordinate analysis, QIIME and LEfSe algorithms.
RESULTS:
There were 25 patients and 25 controls with complete data. Mean age was similar (chronic pelvic pain syndrome 52.3 vs control 57.0 years, p=0.27). For patients with chronic pelvic pain syndrome median symptom duration was 48 months, mean Chronic Prostatitis Symptom Index was 26.0 and mean UPOINT domain was 3.6. Three-dimensional UniFrac principal coordinate analysis revealed tighter clustering of controls in a space distinct from the wider clustering of cases (p=0.001) with cases having decreased alpha diversity (p=0.001). Compared to controls, 3 taxa were overrepresented in cases and 12 were underrepresented, eg Prevotella.
CONCLUSIONS:
Patients with chronic pelvic pain syndrome have significantly less gut microbiome diversity which clusters differently from controls, and robustly lower counts of Prevotella, with separation sufficient to serve as a potential biomarker. The gut microbiome may serve as disease biomarker and potential therapeutic target in chronic pelvic pain syndrome.
Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
gastrointestinal microbiome; pelvic pain; prostatitis
PMID: 26930255 DOI: 10.1016/j.juro.2016.02.2959
[PubMed - in process]
https://www.ncbi.nlm.nih.gov/pubmed/26930255
*****
Microbiomes of Pelvic Pain - ClinicalTrials.gov
https://clinicaltrials.gov/ct2/show/study/NCT01738464
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Microbiomes of Pelvic Pain
This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Northwestern University
Sponsor:
Northwestern University
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
David Klumpp, Northwestern University
ClinicalTrials.gov Identifier:
NCT01738464
First received: November 28, 2012
Last updated: April 6, 2016
Last verified: April 2016
History of Changes
Full Text View Tabular ViewNo Study Results PostedDisclaimerHow to Read a Study Record
Purpose
This research study seeks to provide more insight as to how the microbiome affects or is affected by conditions causing chronic pelvic pain such as Interstitial Cystitis (IC), Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Symptoms (LUTS), or Overactive bladder (OAB). Depression and many chronic pain disorders are often related and are poorly understood, and treatment is often not helpful. The goal of this study is to explain pelvic pain characteristics and causes by studying microbiomes of healthy people compared to people suffering from IC, CP/CPPS, LUTS, OAB, and Major depression.
Condition
Interstitial Cystitis
Chronic Prostatitis
Chronic Pelvic Pain Syndrome
Lower Urinary Tract Symptoms
Overactive Bladder
Major Depression
Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Microbiomes of Pelvic Pain
Resource links provided by NLM:
MedlinePlus related topics: Interstitial Cystitis Pelvic Pain Urine and Urination
U.S. FDA Resources
Further study details as provided by Northwestern University:
Primary Outcome Measures:
Genotype Anaerobic Bacterial populations between Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and Major Depression [ Time Frame: 1 day ] [ Designated as safety issue: No ]
Anaerobic bacteria will be collected from a fecal specimen from both Control patients and patients diagnosed with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and/or Major Depression. Genotyping will be done to differentiate bacterial populations between the Control patients and patients with Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, Overactive Bladder, and/or Major Depression.
Biospecimen Retention: Samples With DNA
Stool specimen
Estimated Enrollment: 300
Study Start Date: June 2012
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
Pelvic Pain
Interstitial Cystitis or Chronic Prostatitis/Chronic Pelvic Pain Syndrome, Lower Urinary Tract Symptoms, and Overactive Bladder patients will be compared to Healthy patients.
Controls
Healthy patients will be used as controls to compare to patients diagnosed with interstitial cystitis, chronic prostatitis, chronic pelvic pain syndrome, Lower Urinary Tract Symptoms, or Overactive Bladder
Major Depression
Major Depressed patients will be compared to Controls and Pelvic Pain cohorts.
Detailed Description:
Interstitial cystitis/painful bladder syndrome (IC), Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Infection Symptoms (LUTS), and Overactive bladder (OAB) are characterized by chronic pelvic pain and voiding dysfunction.These conditions remain an enigma within urology, with no known etiology or widely effective therapies. However, some IC/CP/CPPS/LUTS/OAB and depressed patients suffer bowel co-morbidities, and it is well established that the GI tract can influence bladder function, mood, and sensation via pelvic organ crosstalk. Like other body sites, the gut harbors a rich microflora. It is also well established that IC/CP/CPPS/LUTS/OAB patients often suffer from depression. Therefore, in addition to IC/CP/CPPS/LUTS/OAB patients, we seek patients currently suffering from major depression. Our goal is to identify differences in gut microbiota associated with pelvic pain and determine the mechanisms by which gut microbiota influence gut-brain interactions in pelvic pain. Studies characterizing microbial diversity and relative abundance at a particular body site, the "microbiome," reveal that microbiomes play critical roles in normal cellular and organ function, and thus this importance is emphasized with the Human Microbiome Project (HMP), an NIH Common Fund initiative. Microbiomes are also dynamic and subject to skewing, and these changes are increasingly associated with diseases including Crohn's disease, ulcerative colitis, obesity, and possibly depression. Antibiotic therapies alter microbiomes, often causing temporary dysfunction and sometimes resulting in diseases such as colitis. Since IC/CP/CPPS/LUTS/OAB patients often have a history of urinary tract infection (UTI), they typically receive multiple courses of antibiotics. This therapeutic history of IC/CP/CPPS/LUTS/OAB patients may have adverse consequences for two reasons. First, potential skewing of the gut microbiome may alter normal sensory and functional homeostatic mechanisms, contributing to pain and voiding dysfunction. Second, an altered gut microbiome may foster uropathogen reservoir expansion, and our preliminary data demonstrate urinary E. coli isolates can induce chronic pelvic pain persisting long after microbial clearance. Together these lines of reasoning raise the provocative possibility that microbiomes contribute to IC/CP/CPPS/LUTS/OAB and depression directly by supplying uropathogens or indirectly through organ crosstalk dysfunction. Therefore, is an altered gastrointestinal and/or reproductive tract microbiome associated with these chronic pelvic pain conditions and depression? Our team marries core NIH and NIDDK missions, digestive diseases and kidney/urologic as well psychiatric disciplines, to address this novel question with synergistic expertise in clinical diagnosis of IC/CP/CPPS/LUTS/OAB and depression, quantifying GI tract microbiomes, and neural mechanisms of microbe-induced pelvic pain or depression.
Eligibility
Ages Eligible for Study: 18 Years to 60 Years (Adult)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Sampling Method: Non-Probability Sample
Study Population
Primary care clinic patients Community sample
Criteria
Inclusion Criteria:
Any sex
Between the ages of 18 and 60
Any ethnicity
Have provided informed consent
Physician diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS), interstitial cystitis/painful bladder syndrome (IC/PBS), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), Lower Urinary Tract Symptoms, Overactive Bladder, or Major Depression.
Report symptoms of discomfort or pain in the pelvic or abdominal region of moderate severity for at least a three (3) month period within the last six (6) months, who have been currently diagnosed with major depression
Are healthy, age matched, controls.
Exclusion Criteria:
For IC/CPPS/LUTS/OAB
Evidence of facultative Gram negative or enterococcus with a value of ≥ 100,000 colony forming units (CFU)/milliliter in mid-stream urine (VB2)
Secondary chronic pain condition which would prevent a clear interpretation of the study results
A history of tuberculous cystitis, bladder cancer, carcinoma in situ, or urethral cancer; history of alcohol abuse, inflammatory bowel disease, pelvic radiation or systemic chemotherapy, intravesical chemotherapy, intravesical Bacillus Calmette-Guerin (BCG), active urethral stricture, ureteral calculi, urethral diverticulum, or neurological disease or disorder affecting the bladder or gut
Unlikely to be compliant due to unmanaged medical or psychological conditions, including neurological, psychological or speech/language problems that will interfere or prevent with their understanding of consent
Ability to comply with the protocol or ability to complete the study
Pregnant or Syndromes of Chronic Pelvic Pain (SCPP) symptoms are present only during menses
And if there was antibiotic use in the last 6 months
For Depressed Patients:
Participant is in remission or has recovered from major depression, has substance abuse in the past 6 months, has been diagnosed with any bipolar or psychotic disorder, has been diagnosed with any severe cognitive impairment or dementia, history of cancer (with the exception of skin cancer), has current major psychiatric disorder or other psychiatric or medical comorbidities that would interfere with study participation (e.g. dementia, psychosis, upcoming major surgery, lupus, active heart failure, diabetes, etc., currently has a UTI and/or has had a positive urine culture in the past 6 weeks, and if there was antibiotic use in the last 3 months.
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01738464
Contacts
Contact: David J Klumpp, PhD 312.908.1996 d-kl...@northwestern.edu
Contact: Anthony J Schaeffer, MD 312.908.9844 ajsch...@northwestern.edu
Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: David J Klumpp, PhD Northwestern University
More Information
Responsible Party: David Klumpp, Associate Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT01738464 History of Changes
Other Study ID Numbers: STU00055668 1R24DK094575-01
Study First Received: November 28, 2012
Last Updated: April 6, 2016
Health Authority: United States: Institutional Review Board
Keywords provided by Northwestern University:
Pelvic Pain
Interstitial Cystitis
Microbiome
Prostatitis
Chronic
Depression
Additional relevant MeSH terms:
Depression
Urinary Bladder, Overactive
Depressive Disorder, Major
Lower Urinary Tract Symptoms
Cystitis, Interstitial
Pelvic Pain
Cystitis
Prostatitis
Behavioral Symptoms
Urinary Bladder Diseases
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Pain
Neurologic Manifestations
Prostatic Diseases
Genital Diseases, Male
ClinicalTrials.gov processed this record on December 15, 2016
Copyright Privacy Accessibility Viewers and Players Freedom of Information Act USA.gov
U.S. National Library of Medicine U.S. National Institutes of Health U.S. Department of Health and Human Services
https://clinicaltrials.gov/ct2/show/study/NCT01738464
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Repeated antibiotic use alters gut's composition of beneficial microbes, study shows
SEP 13 2010
David Relman
Repeated use of an antibiotic that is considered generally benign, because users seldom incur obvious side effects, induces cumulative and persistent changes in the composition of the beneficial microbial species inhabiting the human gut, researchers at the Stanford University School of Medicine have found.
By a conservative estimate, something like 1,000 different varieties of microbes coexist harmoniously within a typical healthy person’s gut, said David Relman, MD, professor of medicine and of microbiology and immunology at the medical school and chief of the infectious diseases division at the Veterans Affairs Palo Alto Health Care System. Relman is the senior author of a paper, published online Sept. 13 in Proceedings of the National Academy of Sciences.
The study examined the effects of ciprofloxacin (trade name Cipro), an antibiotic that is widely prescribed for intestinal, urinary and a variety of systemic infections. In an earlier, short-term study, Relman’s group had concluded that people’s intestinal microbial communities seem to bounce back reasonably well within weeks after a five-day regimen of ciprofloxacin. This new study involved two courses of antibiotic administration, six months apart, and it revealed more-subtle, long-term effects of ciprofloxacin use — such as the replacement of multiple resident bacterial species by other, closely related varieties and the occasional complete eradication of a species.
The infrequent occurrence of easily visible side effects such as bloating and diarrhea from ciprofloxacin use has given rise to an assumption that the drug spares most beneficial gut-dwelling bacteria. Overall similarities between pre-regimen gut bacterial strains and their post-regimen replacements explain why such side effects aren’t typically seen after ciprofloxacin use. Still, the more nuanced differences between the pre-existing communities and those that appear in the wake of this repeated disturbance present a new set of problems, said Relman, who is also the Thomas C. and Joan M. Merigan Professor at the medical school. A bacterial species whose presence was lost or diminished may have been performing a valuable job — for example, secreting a protein that’s toxic to a particular pathogen — that is shirked by its replacement. The abandoned function might not be noticed until, perhaps, years later when the pathogen in question invaded the person’s gut.
While the study’s findings shouldn’t be interpreted to mean that ciprofloxacin is dangerous and should be avoided, Relman said, they do raise questions about possible long-term effects of antibiotic administration, in addition to concerns about spurring the evolution of drug-resistant organisms. The new findings underscore the desirability of finding ways to pinpoint not just which bacteria have been lost or whose numbers were diminished by an antibiotic, but also which important beneficial functions performed by the patient’s gut microbial community as a whole have been impaired — such as signaling cells of the intestinal lining, which are constantly turning over, to maintain an appropriate barrier against ingested toxic compounds, or secreting anti-inflammatory substances that may prevent allergic or autoimmune diseases.
For this study, the Stanford scientists collected more than 50 stool samples from each of three healthy adult females over a period of 10 months. Then they used advanced, molecular techniques to count the number of different microbial species represented in each sample, as well as relative population sizes of the different species in that sample.
Twice during this 10-month period, the researchers perturbed their subjects’ gut ecosystems by giving them five-day courses of ciprofloxacin at a standard dose. During the first course, overall bacterial populations in each subject — which had previously waxed and waned but, on the whole, been quite stable — plummeted and remained depressed for about a week. Roughly one-third to one-half of the resident species’ populations declined, with some disappearing entirely. A few originally less-abundant species grew in number, as they filled in the ecological niche abandoned by bugs adversely affected by the drug.
Within a week after the first course’s completion, two of the three subjects’ internal microbial ecosystems had largely returned to a state fairly similar to that before the regimen, as measured by the broad classes to which the microbial constituents belonged. One subject’s overall ecosystem, however, still had not recovered even by that rough measure a full six months later.
The second course of antibiotic administration produced a stronger effect. “Even the one subject whose gut bacterial community fully recovered after the first ciprofloxacin course experienced an incomplete recovery after the second one,” said Relman. The communities in the other two subjects partially recovered from the second course, but never returned to their original state. In essence, each subject’s community of gut-dwelling microbes shifted to a new, “alternative” state and remained in that state for at least two months after the second antibiotic course had been completed. Thus, all three subjects experienced significant and lasting changes in the specific membership of their internal microbial communities at the end of the 10-month study period.
“Ecologists have found that an ecosystem, such as a wildlife refuge, that is quite capable of rebounding from even huge occasional perturbations — forest fire, volcanic eruption, pests — may yet be undone by too rapid a series of such perturbations,” said Les Dethlefsen, PhD, a research scientist in Relman’s lab and the study’s first author. “In the same way, recurring antibiotic use may produce a cumulative effect on our internal microbial ecosystems with potentially debilitating, if as yet unpredictable, consequences.”
“It’s as if your beneficial bacteria ‘remember’ the bad things done to them in the past,” said Relman. “Clinical signs and symptoms may be the last thing to show up.”
The precise counts of gut-dwelling microbes in this study were made possible by a new technique, pioneered in recent years by Relman and others. The older method — growing the microbes in culture — simply doesn’t work for many species and, even when it does, rare species are often swamped by more common ones and don’t get counted. The new technique reads short, telltale DNA snippets that distinguish microbes both from human cells and one from another. This allowed the Stanford researchers to assess both the total number of different microbial varieties and the relative size of each variety’s population.
Similar techniques now make it possible to assess, before and after antibiotic administration, the abundance in a patient’s gut of microbial genes known to code for important functions performed by one or more members of the patient’s gut community, Relman said. In the future, if it becomes known that a key function has been impaired, clinicians might perhaps restore that function by prescribing specific probiotics or nutrients that encourage the return of appropriate beneficial bugs.
The research was supported by a National Institutes of Health Pioneer Award and by the Doris Duke Charitable Foundation. Information about the Departments of Medicine and of Microbiology and Immunology, which also supported the research, is available at http://medicine.stanford.edu and http://microimmuno.stanford.edu.
Bruce Goldman
By
BRUCE GOLDMAN
Bruce Goldman is a science writer for the medical school’s Office of Communication & Public Affairs.
Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children's Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.
https://med.stanford.edu/news/all-news/2010/09/repeated-antibiotic-use-alters-guts-composition-of-beneficial-microbes-study-shows.html
SEP 13 2010
David Relman
Repeated use of an antibiotic that is considered generally benign, because users seldom incur obvious side effects, induces cumulative and persistent changes in the composition of the beneficial microbial species inhabiting the human gut, researchers at the Stanford University School of Medicine have found.
By a conservative estimate, something like 1,000 different varieties of microbes coexist harmoniously within a typical healthy person’s gut, said David Relman, MD, professor of medicine and of microbiology and immunology at the medical school and chief of the infectious diseases division at the Veterans Affairs Palo Alto Health Care System. Relman is the senior author of a paper, published online Sept. 13 in Proceedings of the National Academy of Sciences.
The study examined the effects of ciprofloxacin (trade name Cipro), an antibiotic that is widely prescribed for intestinal, urinary and a variety of systemic infections. In an earlier, short-term study, Relman’s group had concluded that people’s intestinal microbial communities seem to bounce back reasonably well within weeks after a five-day regimen of ciprofloxacin. This new study involved two courses of antibiotic administration, six months apart, and it revealed more-subtle, long-term effects of ciprofloxacin use — such as the replacement of multiple resident bacterial species by other, closely related varieties and the occasional complete eradication of a species.
The infrequent occurrence of easily visible side effects such as bloating and diarrhea from ciprofloxacin use has given rise to an assumption that the drug spares most beneficial gut-dwelling bacteria. Overall similarities between pre-regimen gut bacterial strains and their post-regimen replacements explain why such side effects aren’t typically seen after ciprofloxacin use. Still, the more nuanced differences between the pre-existing communities and those that appear in the wake of this repeated disturbance present a new set of problems, said Relman, who is also the Thomas C. and Joan M. Merigan Professor at the medical school. A bacterial species whose presence was lost or diminished may have been performing a valuable job — for example, secreting a protein that’s toxic to a particular pathogen — that is shirked by its replacement. The abandoned function might not be noticed until, perhaps, years later when the pathogen in question invaded the person’s gut.
While the study’s findings shouldn’t be interpreted to mean that ciprofloxacin is dangerous and should be avoided, Relman said, they do raise questions about possible long-term effects of antibiotic administration, in addition to concerns about spurring the evolution of drug-resistant organisms. The new findings underscore the desirability of finding ways to pinpoint not just which bacteria have been lost or whose numbers were diminished by an antibiotic, but also which important beneficial functions performed by the patient’s gut microbial community as a whole have been impaired — such as signaling cells of the intestinal lining, which are constantly turning over, to maintain an appropriate barrier against ingested toxic compounds, or secreting anti-inflammatory substances that may prevent allergic or autoimmune diseases.
For this study, the Stanford scientists collected more than 50 stool samples from each of three healthy adult females over a period of 10 months. Then they used advanced, molecular techniques to count the number of different microbial species represented in each sample, as well as relative population sizes of the different species in that sample.
Twice during this 10-month period, the researchers perturbed their subjects’ gut ecosystems by giving them five-day courses of ciprofloxacin at a standard dose. During the first course, overall bacterial populations in each subject — which had previously waxed and waned but, on the whole, been quite stable — plummeted and remained depressed for about a week. Roughly one-third to one-half of the resident species’ populations declined, with some disappearing entirely. A few originally less-abundant species grew in number, as they filled in the ecological niche abandoned by bugs adversely affected by the drug.
Within a week after the first course’s completion, two of the three subjects’ internal microbial ecosystems had largely returned to a state fairly similar to that before the regimen, as measured by the broad classes to which the microbial constituents belonged. One subject’s overall ecosystem, however, still had not recovered even by that rough measure a full six months later.
The second course of antibiotic administration produced a stronger effect. “Even the one subject whose gut bacterial community fully recovered after the first ciprofloxacin course experienced an incomplete recovery after the second one,” said Relman. The communities in the other two subjects partially recovered from the second course, but never returned to their original state. In essence, each subject’s community of gut-dwelling microbes shifted to a new, “alternative” state and remained in that state for at least two months after the second antibiotic course had been completed. Thus, all three subjects experienced significant and lasting changes in the specific membership of their internal microbial communities at the end of the 10-month study period.
“Ecologists have found that an ecosystem, such as a wildlife refuge, that is quite capable of rebounding from even huge occasional perturbations — forest fire, volcanic eruption, pests — may yet be undone by too rapid a series of such perturbations,” said Les Dethlefsen, PhD, a research scientist in Relman’s lab and the study’s first author. “In the same way, recurring antibiotic use may produce a cumulative effect on our internal microbial ecosystems with potentially debilitating, if as yet unpredictable, consequences.”
“It’s as if your beneficial bacteria ‘remember’ the bad things done to them in the past,” said Relman. “Clinical signs and symptoms may be the last thing to show up.”
The precise counts of gut-dwelling microbes in this study were made possible by a new technique, pioneered in recent years by Relman and others. The older method — growing the microbes in culture — simply doesn’t work for many species and, even when it does, rare species are often swamped by more common ones and don’t get counted. The new technique reads short, telltale DNA snippets that distinguish microbes both from human cells and one from another. This allowed the Stanford researchers to assess both the total number of different microbial varieties and the relative size of each variety’s population.
Similar techniques now make it possible to assess, before and after antibiotic administration, the abundance in a patient’s gut of microbial genes known to code for important functions performed by one or more members of the patient’s gut community, Relman said. In the future, if it becomes known that a key function has been impaired, clinicians might perhaps restore that function by prescribing specific probiotics or nutrients that encourage the return of appropriate beneficial bugs.
The research was supported by a National Institutes of Health Pioneer Award and by the Doris Duke Charitable Foundation. Information about the Departments of Medicine and of Microbiology and Immunology, which also supported the research, is available at http://medicine.stanford.edu and http://microimmuno.stanford.edu.
Bruce Goldman
By
BRUCE GOLDMAN
Bruce Goldman is a science writer for the medical school’s Office of Communication & Public Affairs.
Stanford Medicine integrates research, medical education and health care at its three institutions - Stanford University School of Medicine, Stanford Health Care (formerly Stanford Hospital & Clinics), and Lucile Packard Children's Hospital Stanford. For more information, please visit the Office of Communication & Public Affairs site at http://mednews.stanford.edu.
https://med.stanford.edu/news/all-news/2010/09/repeated-antibiotic-use-alters-guts-composition-of-beneficial-microbes-study-shows.html
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