Probiotic in emotional symptoms of CFS -Full

[Guest guest]

This study was done using people whom have CFS - however there are many

disorders and illnesses which include digestive issues. In my opinion, the

results of this study would apply to all of those with these digestive issues

regardless what disorder or illness they have. One of the wonders of the

internet and health groups is that we can all learn from each

other...........

This has attached a pdf file of the full study - for those whom can

access it.

blessings

Shan

 

forwarded.........

 

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Reference:

Probiotic in emotional symptoms of CFS

Help ME Circle, 1 June 2009, Abstract,

Co-Cure: _http://bit.ly/14yE8f_ (http://bit.ly/14yE8f)

 

The researchers below used the *best* Canadian ME/CFS criteria:

_http://bit.ly/13FRXv_ (http://bit.ly/13FRXv)

 

Thanks to Tom Kindlon <_tomkindlon_

(tomkindlon) >

 

~jan van roijen

 

````````

Gut Pathogens 2009, 1:6

_http://bit.ly/AbA2p_ (http://bit.ly/AbA2p)

 

doi:10.1186/1757-4749-1-6

 

A randomized, double-blind, placebo-controlled pilot study of a probiotic

in emotional symptoms of chronic fatigue syndrome

 

A Venket Rao1, Alison C Bested2,3, Tracey M Beaulne3, Martin A Katzman4,5,

Christina Iorio5, John M Berardi6 and Alan C Logan3

 

1. Department of Nutritional Sciences, University of Toronto, 50 College

Street, Toronto, Ontario M5S 3E2, Canada

2. Environmental Health Clinic, Women's College Hospital, 76 Grenville

Street, Toronto, Ontario M5S 1B2, Canada

3. Integrative Care Centre of Toronto, 3600 Ellesmere Road, Unit 4,

Toronto, Ontario M1C 4Y8, Canada

4 Department of Psychiatry, University of Toronto, 250 College Street,

Toronto, Ontario M5T 1R8, Canada

5. START Clinic for Mood and Anxiety Disorders, 790 Bay Street, Toronto,

Ontario M5G 1N8, Canada

6. Precision Nutrition, 1665 Gregory Road, St Catharines, Ontario L2R6P9,

Canada

 

Received: 3 October 2008

Accepted: 19 March 2009

Published: 19 March 2009

 

© 2009 Rao et al; licensee BioMed Central Ltd. This is an Open Access

article distributed under the terms of the Creative Commons Attribution License

( _http://creativecommons.org/licenses/by/2.0_

(http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use,

distribution, and

reproduction in any medium, provided the original work is properly cited.

 

 

Abstract

 

Chronic fatigue syndrome (CFS) is complex illness of unknown etiology.

Among the broad range of symptoms, many patients report disturbances in the

emotional realm, the most frequent of which is anxiety. Research shows that

patients with CFS and other so-called functional somatic disorders have

alterations in the intestinal microbial flora. Emerging studies have suggested

that pathogenic and non-pathogenic gut bacteria might influence mood-related

symptoms and even behavior in animals and humans. In this pilot study, 39

CFS patients were randomized to receive either 24 billion colony forming

units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two

months. Patients provided stool samples and completed the Beck Depression

and Beck Anxiety Inventories before and after the intervention. We found a

significant rise in both Lactobacillus and Bifidobacteria in those taking the

LcS, and there was also a significant decrease in anxiety symptoms among

those taking the probiotic vs controls (p = 0.01). These results lend further

support to the presence of a gut-brain interface, one that may be mediated

by microbes that reside or pass through the intestinal tract.

 

``

Background

 

Chronic Fatigue Syndrome (CFS) is a medically unexplained illness,

characterized by persistent and relapsing fatigue [1,2]. This severe

pathological

fatigue is worsened by periods of physical and mental exertion. Along with

the ongoing fatigue, it has also been noted that 97% of CFS patients report

neuropsycho- logical disturbances. This can manifest as cognitive

dysfunction, sleep disturbances, headaches, and a variety of symptoms in the

emotional realm. Of these emotion-related symptoms, anxiety and depression are

the

most prevalent, with approxima- tely half or patients meeting the criteria

for an anxiety disorder or major depressive disorder. Over 40% of patients

report symptoms that are often part of anxiety and depressive disorders,

including dizziness, lightheadedness, heart palpitations, sleep

disturbances, appetite changes and shortness of breath [3].

 

 

Many CFS patients also complain of gastrointestinal (GI) disturbances.

Indeed, patients with CFS are more likely to report a previous diagnosis of

irritable bowel syndrome (IBS), meet diagnostic criteria for IBS and

experience IBS related symptoms [4]. While CFS is neither a gastrointestinal

nor

psychiatric disorder per se, over 50 percent of patients with CFS meet the

diagnostic criteria of IBS, and anxiety itself is often a hallmark symptom in

those with IBS [5]. Although the mechanisms behind this frequent overlap

with IBS are far from understood, some investigators have documented that

there are marked alterations in the intestinal microflora of CFS patients,

with lower levels of Bifidobacteria and higher levels of aerobic bacteria

[6].

 

 

Recently it was discovered that gut pathogens in the GI tract can

communicate with the central nervous system and influence behavior associated

with

emotion, anxiety in particular, even at extremely low levels and in the

absence of an immune response [7,8]. Researchers have also shown that the

administration of certain bacteria found in soil may support resilience and

positively alter stress-related emotional behavior in animals under

experimental stress [9]. In addition, so-called probiotics, or live

microorganisms

which confer a health benefit on the host, have the potential to influence

mood- regulating systemic inflammatory cytokines, decrease oxidative stress

and improve nutritional status when orally consumed [6].

 

 

This background led some investigators to hypothesize a possible

adjunctive therapeutic role of probiotic bacteria in mood-related psychiatric

symptoms [10]. Some hints at the utility of probiotics for mood regulation come

from a recent human trial involving the administration of Lactobacillus

casei strain Shirota (LcS) or placebo to 132 otherwise healthy adults. In an

intriguing finding, the investigators discovered that those with the lowest

scores in the depressed/ elated dimension at baseline had significant

improvement in mood scores after taking the probiotic compared to the placebo

group. The probiotic bacteria and placebo were unable to make a difference in

those with the highest baseline mood scores [11]. In addition, ongoing

experimental studies in this area have recently shown that in the animal

model of depression, the oral administration of a probiotic can increase plasma

tryptophan levels, decrease serotonin metabolite concentrations in the

frontal cortext and dopamine metabolite concentrations in the amygdaloid cortex

[12].

 

 

With this background, the current investigation was initiated to determine

if orally administered probiotics could make a difference in symptoms of

depression and anxiety in adult patients with chronic fatigue syndrome.

 

 

Brief Report

 

 

Candidates for inclusion were screened from a pool of CFS patients in a

tertiary setting. Those adult patients aged 18–65 meeting the formal

diagnostic criteria for CFS, according to published guidelines, [13] were

further

screened for inclusion based on suitability to complete a two month trial.

Excluded were those patients with unstable physical illness and those with a

severity of CFS such that they were largely bedridden. Also excluded were

patients meeting criteria for psychiatric disorders other than depression

and/or anxiety. The study was approved by the institutional review board of

the University of Toronto. Patients meeting inclusion criteria provided

written, informed consent at the screening visit after the procedures had been

fully explained.

 

 

CFS patients who met all inclusion/exclusion criteria were evaluated using

the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI).

Patients also provided stool samples, taken over 3 days, at the evaluation

phase. Kits were provided to the patients according to guidelines of

appropriate collection as per the University of Toronto, School of Medicine,

Department of Nutritional Sciences. Samples were sent to the Fecal Laboratory of

the University of Toronto, Department of Nutrition for evaluation. Using

culture technique, the stool samples were assessed for total aerobe,

anaerobe, Lactobacillus spp, and Bifidobacteria spp counts.

 

 

After collection of the data and samples at the initial evaluation phase,

39 CFS patients were randomized to begin an intervention phase, an

eight-week period where each patient consumed either a specific lactic acid

probiotic bacteria or placebo by mouth. After each main meal, or three times

daily, patients consumed the contents of an unmarked sachet containing 8

billion

colony forming units (cfu) of Lactobacillus casei strain Shirota (LcS) or

a placebo with identical taste and appearance. Each CFS patient in the

active intervention group consumed a total of 24 billion cfu of LcS probiotic

per day. Follow-up evaluation phase: After 8 weeks of intervention, LcS or

placebo, subjects were re-evaluated by completion of the BDI and BAI, and a

second stool analysis was conducted using the same collection and culture

methods.

 

 

Thirty five CFS patients, 27 females and 8 males, completed the 8-week

investigation. Four patients, two from the LcS probiotic group and two from

the placebo group, withdrew from the study for reasons unrelated to the

intervention. The LcS probiotic powder was well tolerated and there were no

significant adverse events reported in the probiotic or placebo groups.

Compared to the placebo control group, the treatment group showed moderate

increases in fecal total aerobes and anaerobes and significant increases in

fecal

total Bifidobacteria and Lactobacillus (Figure 1). Among the Placebo group

only 37.5% of subjects showed an increase in Bifidobacteria and 43.8% in

Lactobacillus compared to 73.7% and 73.7% in the treatment group respectively

(Table 1). The number of subjects showing changes in fecal Bifidobacteria

and Lactobacillus is also presented in Table 2. An increase in the number of

fecal Lactobacillus observed in this study was to be expected since the

probiotic sachets contained high levels of a specific strain of this

bacteria. The positive results observed with respect to Bifidobacteria are very

encouraging since Bifidobacteria levels have been reported to be low in CFS,

and they are generally associated with a healthy colonic environment. [14].

It can therefore be concluded that ingestion of the probiotic capsules

contributed towards the predo- minance of bacteria that are associated with a

healthy gastrointestinal system.

 

 

Figure 1. Difference in fecal bacteria between 0 ands 8 weeks in placebo

and treatment groups: _http://bit.ly/F3ArG_ (http://bit.ly/F3ArG)

 

 

Table 1. Total Fecal Aerobes, Anaerobes, Bifidobacteria and Lactobacillus

in Placebo and Treatment Groups: _http://bit.ly/CHF3A_ (http://bit.ly/CHF3A)

 

 

 

Table 2. Number of Subjects Showing Changes in Fecal Bifidobacteria and

Lactobacillus: _http://bit.ly/2IpRUZ_ (http://bit.ly/2IpRUZ)

 

 

When evaluating the BDI and BAI for changes over the course of the 8-week

study, we found a statistical difference between the anxiety scores in

those taking LcS or the placebo.

Overall there was a significant improvement in anxiety among those taking

the active LcS compared to the placebo (Table 3). The differences as

assessed by the BDI did not reach statistical significance among those taking

the

active LcS.

 

 

Table 3. Repeated measures analysis of variance for the BDI and BAI after

treatment with placebo or probiotics: _http://bit.ly/2EcnlI_

(http://bit.ly/2EcnlI)

 

 

Discussion

 

 

The idea that implanting the intestines with Lactobacillus strains may

improve quality of life and mental health is not a new one. Dr. George Porter

Phillips first reported in 1910 that although Lactobacillus tablets and

powder were ineffective, a gelatin-whey formula with live lactic acid bacteria

improved depressive symptoms in adults with melancholia [15]. In a series

of case reports, separate researchers concluded in 1923 that 'the

administration of acidophilus milk is recommended in the treatment of psychoses

as a

means to physical betterment' [16]. In this pilot study we found that the

oral administration of Lactobacillus casei strain Shirota (LcS, Yakult

Honsha, Tokyo, Japan) caused a significant rise in fecal Bifidobacteria spp.

and

Lactobacillus spp. The rise in Lactobacilli was an expected finding,

although the concomitant rise in Bifidobacteria suggests that there may be far

reaching effects of oral probiotics on other microbial residents of the

gastrointestinal tract. This finding supports previous research showing that

the oral administration of Lactobacillus plantarum 299 V caused a

significant rise in fecal Bifidobacteria levels [17]. In this case the elevation

of

Bifidobacteria levels should be considered a positive finding, particularly

when considering that Bifidobacteria levels may be low in CFS. Also of

relevance is a recent experimental study which has shown that a specific strain

of Bifido- bacteria can boost plasma tryptophan levels and alter serotonin

and dopamine turnover in areas of the brain associated with depression and

anxiety [12]. We also found a significant reduction in anxiety scores among

those CFS patients consuming the LcS bacteria. The group differences in

anxiety are noteworthy since anxiety is a frequent mental health symptom

reported by CFS patients.

 

 

In recent years the interface between neuropsychiatry and gastroenterology

has converged into a new discipline referred to as enteric neuroscience.

Emerging studies have shown that intestinal bacteria may directly

communicate with the central nervous system by way of the vagal sensory nerve

fibers

and the peripheral immune system. Indeed, experimental studies have shown

that even minute doses of microbes within the gastrointestinal tract, levels

that do not trigger an immune response, are capable of influencing

neurotransmission in the paraventricular hypothalamus, the central nucleus of

the

amygdala, and the bed nucleus of the stria terminalis [8]. All three of

these regions are involved in the processing of emotions related to anxiety and

mood. It is also true that quantitative alterations in the make-up of

gastrointestinal microbes are a consequence of states of stress and fear, and

alterations in the gut microflora have recently been associated with impaired

glucose control and obesity [18,19].

 

 

More hints of a connection between intestinal microflora and brain

function come from studies in the autistic spectrum. Research has shown marked

alterations of the gastrointestinal microflora in autism, with specific

elevations in various Clostridium spp. [20]. Some researchers speculate that

low-grade chronic intestinal inflammation induced by elevations in bacteria

such

as potentially pathogenic Clostridium spp may be directly influencing brain

centers. Experimental studies show that indeed chronic gut inflammation

leads to activation of areas of the brain associated with mental health and

behavioral disorders, including the hypothalamus, amygdala and cortical

centers [21]. While we did not look specifically at Clostridium spp. in this

pilot investigation, it has been noted that Lactobacillus can competitively

displace Clostridium and other potentially pathogenic gut bacteria [22].

Propionic acid is a short chain fatty acid produced primarily by Clostridium

and

Bacteroides spp.; emerging research suggests that this acid may be

involved in anxiety. Elevated production of propionic acid in the gut has been

shown to increase behaviors associated with anxiety and aggression in animals

[23].

It has also been shown recently that when propionic acid gains access to

the brain it can impair the social behavior of animals. Changes to the

animal behavior include decreased playful behavior, increasing social isolation,

and an increase in repetitive behaviors that may indicate anxiety [24].

While human data is lacking, a study in animals did show that the LcS as used

in our study can lower cecal propionate levels [25].

 

 

Some researchers have stated that the so-called 'hygiene hypothesis'

extends into the realm of mental health disorders as well. The hygiene

hypothesis

is the proposition that the documented rise in chronic inflammatory

disorders (allergies, autoimmunity, and inflammatory bowel disease) within

developed countries is driven by a changing microbial environment, an absence

of

beneficial bacteria that has in turn altered the immuno-regulatory circuits

which normally keep inflammatory responses in check [26].

Many mental health conditions, and so-called functional somatic disorders

such as CFS, have been well-documented to have elevations in inflammatory

cytokines, and these inflammatory cytokines at even low levels can produce

symptoms of anxiety and depression in otherwise healthy adults [26].

Therefore, since orally administered probiotics can decrease inflammatory

cytokines

in humans, it has been postulated that bacteria may be used to positively

influence mood in patient populations where both emotional symptoms and

inflammatory immune chemicals are elevated [10]. It is becoming increasingly

clear that anxiety and stress itself may lower levels of fecal lactic acid

bacteria, and this, in turn, may compromise various aspects of health [27].

 

 

Overall the results suggest that specific strains of probiotic bacteria

may have a role to play in mediating some of the emotional symptoms of CFS

and other related conditions. However, it is important to note that this is a

small pilot study and broad conclusions cannot be drawn at this time.

Since we did not evaluate bowel function during the study, it is entirely

possible that the decreased anxiety was a consequence of improved bowel

function. In an unexplained medical condition such as CFS, where over 70% of

patients meet the criteria for IBS, it is possible that regulation of bowel

movements made a difference in mental state.

Indeed LcS has been shown to regulate bowel function and decrease

constipation in a controlled trial [28]. It is also true that LcS has been

shown to

reduce small intestinal bacterial overgrowth and the subjective reporting

of the passage of gas in patients with IBS [29]. This is of significance

because SIBO and intestinal permeability often overlap, and patients with

chronic fatigue syndrome are known to have both increased intestinal

permeability and SIBO. Indeed, correction of SIBO and intestinal permeability

has

been shown to improve symptoms in CFS and depressive disorders [30,31].

Therefore, it is entirely possible that our results are an artifact of improved

gut structure and function via the LcS restoration of a healthy intestinal

biofilm. However, a recent study using the same LcS strain in healthy adults

suggests that there may be a more direct microbial influence on emotional

state. In healthy adults who were reported to be more depressed/less elated

in daily functioning at baseline, there was significant improvement in mood

scores after taking the probiotic. In that controlled trial the

improvements in mood were not related to changes in bowel function [11].

 

 

This preliminary research raises many questions regarding possible

mechanisms whereby probiotics might influence anxiety and depression. The

results

of the present study should be viewed simply as a stimulus for further

research. Follow-up studies with probiotics should further examine specific gut

microbes, intestinal structure and function as well as physiological

markers associated with anxiety and depression. These may include inflammatory

cytokines and other immune chemicals, blood tryptophan levels and urinary

metabolites of neurotransmitters.

 

 

Competing interests

 

This pilot study was funded by Yakult Honsha, Tokyo, Japan. None of the

authors have any financial relationship with the funding body, Yakult Honsha,

and have no interest in the sales of this product under investigation.

 

Authors' contributions

 

AVR coordinated the study, completed the stool analysis and data analysis,

ACB and TMB performed the patient recruitment, screening, sample and data

collection, MK, CI and JMB collected and evaluated the BDI and BAI

questionnaires and completed the data analysis, ACL designed the investigation

and

drafted the manuscript. All authors reviewed the data and content, assisted

in the final manuscript construction and agree to its content.

 

 

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~~~~~~~~

 

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Send an Email for free membership

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