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Showing posts with label Probiotics. Show all posts
Showing posts with label Probiotics. Show all posts

Thursday 29 September 2016

Probiotics – Science and Pseudoscience


Once anyone starts to make claims that some autism is treatable, people respond in different ways.  Those applying what has always been taught in medical school, that autism is untreatable,  will either think you are making it all up, or worse, you are some evil person taking advantage of parents in emotional distress.

The very few people who read the research about things like metabolic errors and intracellular signaling may well take a different view. Also the oncology/cancer researchers who themselves think about sub-types of disease that are induced by specific signaling pathways (like RAS-induced cancers for example), may well see the sense in experimentation like that in this blog.

Medicine does indeed say that autism, Down Syndrome and ID/MR are untreatable; however current science does not support this.  Your local doctor applies medicine; he is likely totally out of his depth when it comes to where science is in 2016.

My posts are just my take on the science, I am well aware that some clever neurologists have looked at this blog and think it is all fantasy.  The doctors who have a child with autism and read this blog tend to look from a different perspective and with a much more open mind.  Once you find one therapy that is truly effective, bumetanide in our case, then there can be no turning back.

There are all kinds of diets, supplements and therapies promoted by various people, I wish them all well.

The problem any future science-based autism clinicians will have is that they inevitably get mixed up with other types.  In the US they already go to the same autism conferences, which surprises me. People then think, "Oh well if Professor X is here from Ivy League college Y, then everyone must be legit".  Big mistake. You need to be on really top form to separate out all the pseudoscience, and on occasion you may get it wrong. 


Probiotics

I used to be a skeptic of probiotic bacteria, that is until I was prescribed some little glass vials about a dozen years ago.  I had some side effect from an antibiotic prescribed for an ear infection.  I still recall the ENT doctor calling out (not in English) and asking what to prescribe for the GI side effects.  When I took his prescription to the pharmacy I received a pack of glass vials and a small saw blade.  You used the saw to cut the neck of the vial then you added water to the white fungus growing in the vial and poured into a glass of water, which you then drank.

It most definitely worked.

Even today when I tell my doctor relatives in the UK that probiotics work wonders for diarrhea, all I get is strange looks.

So I am already sold on the fact that probiotic bacteria can do great things for stomach problems.

I spoke to a friend in Denmark this week who has been ill much of the year and finally his problems have been diagnosed as stemming from Ulcerative Colitis.  His first symptom was actually a blood clot.  It turns out that inflammatory bowel diseases (IBD), like ulcerative colitis, increase your risk of blood clots.

So I told my friend to read up on VSL#3 and Viviomixx, which do seem to help IBD, and also to read up on melatonin in the IBD research.


Probiotics and Inflammatory Disease

Looking at immune health more generally we saw how the probiotic Miyairi 588 is used to produce butyric acid which can improve immune health.  This is why cost conscious farmers put it in their animal feed to produce healthier, faster growing animals.

We saw that an alternative is just to add sodium butyrate to the food.  This is done is both livestock and some humans.

Butyrate is an HDAC inhibitor and so is thought to have epigenetic effects.

Probiotics and the Brain

You might be able to convince your doctor that a probiotic bacterium can be good for your stomach, but would you convince him that it could be good for the brain?

I must admit I also would like to see some scientific evidence, beyond anecdotes - even my own anecdotes.

So finally today’s featured scientific study:-




 There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.

The study is interesting because it shows that a bacterium can modify GABA subunit expression in the brain, but when the vagus nerve is removed the effect is lost.  So it is pretty likely that in humans the vagus nerve is the conduit to the brain, as has many times been suggested, but here we have some pretty conclusive supporting evidence.

For a less science heavy explanation of the study:-

Belly bacteria boss the brain

Gutmicrobes can change neurochemistry and influence behavior




I did a post about the vagus nerve a while back and there is an easy to read article here:-

Viva vagus: Wandering nerve could lead to range of therapies




My old posts:-

The Vagus Nerve and Autism


Cytokine Theory of Disease & the Vagus Nerve




Conclusion

Individual GI bacteria have very specific effects.  In people with neurological dysfunctions the possibility genuinely exists to delivery therapies to brain via the gut.  This might have been seen as pseudoscience a decade ago, but now it is part of science, but not yet medicine.

Many other clever things going on in your gut.  The long awaited CM-AT pancreatic enzyme therapy, from a company called Curemark, is now entering its phase 3 trial (thanks Natasa). Click below. 

Blüm is the study of CM-AT, a biologic, for the treatment of Autism.



  
The Curemark lady, Joan Fallon, has collected numerous patents regarding various mixtures of pancreatic enzymes and even secretin.  Secretin was an autism therapy that was written off many years ago, but is still used by some DAN type doctors.

Some comments on this blog from parents of kids in the early CM-AT trials are supportive of its effect.

Pancreatic enzymes (e.g. Creon) are already used as a therapy for people who lack pancreatic enzymes and many people with autism have taken them.


Curemark have never published any of their trial data which annoys at least one of our medical researcher readers.  If you have so many patents, why not share your knowledge?






Thursday 15 September 2016

Improvement in core ASD symptoms after long-term treatment with probiotics




Another brief post today to draw your attention to a paper highlighted on the Questioning Answers blog.

There are two virtually identically probiotics one called VSL#3 and the other called Viviomixx.  As pointed out in a recent post there is an ongoing clinical trial of Vivomixx.

  

Ongoing Clinical Trial of Vivomixx Probiotic in Children with Autism




Some readers of this blog are trialing VSL#3 or Viviomixx.

The new paper is a case study of a 12 year old boy with severe autism who was given VSL#3 at his residential care home.

He has celiac disease, but his doctors were surprised that when the reduction in severity of abdominal symptoms was accompanied by an improvement in his autism.

This should not come as a surprise to regular readers.  Just recall Kanner’s subject #1, Donald Triplett, who was later diagnosed with juvenile arthritis. When his arthritis was treated his autism improved.  This is exactly what should be expected.

Treat your comorbidities, particularly those of an inflammatory/auto immune nature, and very likely you will improve behavior and even cognition.





Abstract

Objectives: Autism spectrum disorder is a neurodevelopmental condition that typically displays socio-communicative impairment as well as restricted stereotyped interests and activities, in which gastrointestinal disturbances are commonly reported. We report the case of a boy with Autism Spectrum Disorder (ASD) diagnosis, severe cognitive disability and celiac disease in which an unexpected improvement of autistic core symptoms was observed after four months of probiotic treatment.
Method: The case study refers to a 12 years old boy with ASD and severe cognitive disability attending the Villa Santa Maria Institute in resident care since 2009. Diagnosis of ASDs according to DSM-V criteria was confirmed by ADOS-2 assessment (Autism Diagnostic Observation Schedule).
The medication used was VSL#3, a multi-strain mixture of ten probiotics. The treatment lasted 4 weeks followed by a four month follow-up.
The rehabilitation program and the diet was maintained stable in the treatment period and in the follow up. ADOS-2 was assessed six times: two times before starting treatment; two times during the treatment and two times after interruption of the treatment.
Results: The probiotic treatment reduced the severity of abdominal symptoms as expected but an improvement in Autistic core symptoms was unexpectedly clinically evident already after few weeks from probiotic treatment start. The score of Social Affect domain of ADOS improved changing from 20 to 18 after two month’s treatment with a further reduction of 1 point in the following two months. The level 17 of severity remained stable in the follow up period. It is well known that ADOS score does not fluctuate spontaneously along time in ASD and is absolutely stable.
Conclusions: The appropriate use of probiotics deserves further research, which hopefully will open new avenues in the fight against ASD.








Friday 8 July 2016

Ongoing Clinical Trial of Vivomixx Probiotic in Children with Autism


Since there is now interest in the potential benefit of probiotic bacteria to treat some autism, I wanted to point out that there actually is a clinical trial underway in Italy.  It is funded the Italian Ministry of Health and by the Tuscany Region.  They use Vivomixx, an OTC probiotic from the Italian speaking region of Switzerland.   


Vivomixx contains:
Streptococcus thermophilus DSM 24731, bifidobacteria (B. breve DSM 24732, B. longum DSM 24736, B. infantis DSM 24737) 
lactobacilli (L. acidophilus DSM 24735, L. plantarum DSM 24730, L. paracaseiDSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734).


Before you start wondering, it is not cheap; the Swiss do not do cheap.

There is a detailed explanation of the trial in the full version of the paper below.  It is due to be completed at the end of 2017.
  
Vivomixx is virtually identical to a well known expensive probiotic called VCL#3, which has been used in research.  Due to some dispute the originator of VCL#3 started a new company which now sells Vivomixx.  In some countries one is available and in other countries it is the other one.  VCL#3 is even more expensive. 


Background

A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a “gut-brain axis” disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD.

Methods

A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns.

Discussion

The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD.

Trial registration

ClinicalTrials.gov Identifier: NCT02708901. Retrospectively registered: March 4, 2016.


So in the coming years it looks like there will be some actual data with which you can decide whether or not to trial specific probiotic bacteria. 
Hopefully, the Biogaia people in Sweden will provide their products for some independent researchers to trial on humans with autism, probably Swedish ones.








Saturday 2 July 2016

Biogaia Trial for Inflammatory Autism Subtypes



UPDATE: A significant minority of parents report negative reaction to Bio Gaia, this seems to relate to histamine; but more than 50% report very positive effects without any side effects; so best to try a very small dose initially to see if it is not well tolerated. 
Histamine Reaction to Bio Gaia gastrus


Alli, our reader from Switzerland, has established that a large daily dose (5 tablets a day, cycled 3 weeks on and 3 weeks off) of the Biogaia Gastrus probiotic has a positive effect on the inflammatory sub-type of her son’s autism and also in other people she has shared her therapy with.  There is plenty of science to support its use.

In earlier posts I looked at a different probiotic bacteria (Clostridium butyricum Miyairi 588) that is widely used in animals to improve auto-immune health.  That bacteria is used in humans, but as is the case with BioGaia Gastrus, the focus is on stomach health not auto immunity.  Nobody has proposed an effective dose of Miyairi 588 in human autism; I have only used it in small doses.

It turns out that there is vast wealth of research into the effects of specific probiotic bacteria.  The research is really very interesting for anyone with any kind of allergy.  I expect that, as Alli found, the potential therapeutic benefit goes far wider, to many kinds of inflammatory disease outside the gut, particularly the very hard to treat ones, perhaps even MS (multiple sclerosis).


Biogaia and Lactobacillus Reuteri 

Lactobacillus reuteri is a species of bacteria that belongs to one of the major lactic-acid producing genera of bacteria. It can be found in the human intestinal tract, though not always and often in relatively low numbers. Lactobacillus reuteri is also found in the gut of other mammals and birds.
Initially, Lactobacillus reuteri was used to treat necrotizing colitis, a gastrointestinal disease characterized by infection and inflammation that is particularly dangerous for infants, particularly those born prematurely. Lactobacillus reuteri was used due to its anti-inflammatory effects.
The research on Lactobacillus reuteri and necrotizing colitis used the Lactobacillus reuteri strains ATCC 55730 and its daughter strain DSM 17938, both of which can survive oral supplementation.
Interest in Lactobacillus reuteri grew after research confirmed that changing aspects of the digestive system can influence the immune system. A strain of Lactobacillus reuteri called ATCC PTA 6475 has been found to improve levels of testosterone and oxytocin, as well as skin quality in animal studies. Research on animals has also found potential benefits for hair quality, bone mass and preventing weight gain from obesity-causing diets.
One of the ways Lactobacillus reuteri may work involves a kind of T cell called a Treg cell (a T cell that down-regulates the immune system in part by producing a cytokine called IL-10). Lactobacillus reuteri increases the amount of Treg cells in the body, which suppresses the actions of another kind of T cell called a Th17 cell (which secretes IL-17). Preserving or reversing this process (either by increasing IL-10 or by blocking IL-17) appears to provide therapeutic benefits.
Lactobacillus reuteri increases the number of Treg cells in the intestines, which can then be absorbed back into the blood to benefit the rest of the body.


BioGaia Gastrus is a combination of the well-researched probiotic strain Lactobacillus reuteri17938 (Lactobacillus reuteri Protectis) and the anti-inflammatory strain Lactobacillus reuteri ATCC PTA 6475. It contains 200 million CFU of live bacteria.

The original Biogaia product is called BioGaia Protectis; it only contains Lactobacillus reuteri 17938 (Lactobacillus reuteri Protectis).  It contains 100 million CFU of live bacteria.

Since some readers are already trialing Alli’s therapy, I thought it would be useful to have a single place on this blog where people could leave feedback.  Here is her explanation:-



Dear all,

Lactobacillus Reuteri ATCC 55730 was initially discovered and sourced from women from Peru who carried this strain in their breast milk. 

"The first strain of Lactobacillus reuteri for human use was isolated in 1990 from the breast milk of a Peruvian mother living in the Andes. This strain was deposited at the American Type Culture Collection (ATCC) as Lactobacillus reuteri SD 2112 (SD = safety deposit), and was later given the number ATCC 55730.

In 2007 Lactobacillus reuteri ATCC 55730 was replaced by the “daughter strain” Lactobacillus reuteri DSM 17938. The only difference between the strains is the loss of two plasmids of ATCC 55730 that carried resistance to tetracycline and lincomycin, respectively."http://www.biogaia.com/history-lactobacillus-reuteri

Through my personal review of immunology literature and ASD/immunity related literature and documenting crossroads between immune pathways and Mtor pathways, I came to the conclusion more than one year ago that this was a very interesting strain to try on my son with ASD and a TH1 profile. Biogaia Gastrus was only available in Korea and Italy at the time so I ordered it from an Italian pharmacy online.
It has helped my son significantly in combination with other interventions.

The mechanism at stake is probably the following:

- downregulation of TH1 through upregulation of IL-10 and downregulation of IL-17
This prevents autoimmune phenomena and cytokine flares which affect cognition in certain subtypes of ASD. However, the downside is that long term intake also impairs one's immune system's capacity to fight off infections... 

We use Biogaia on and off for 3 week periods- at a dosage of 5 tablets a day (less is useless in terms of potency).

Use must be stopped if a child shoes any sign of infection.

I have shared this over the past year with several parents around me who have children with similar subtypes and they report similar results.



Effect of Lactobacillus reuteri 17938 on Monty

My son Monty, aged 12 with autism, pollen allergy and occasional asthma, was again my willing test subject.  This is the worst time of the year when his allergy triggers asthma and autism flare-ups.

Where we live, only the older version of Biogaia is sold.  So he has been taking Lactobacillus reuteri 17938, 400 million CFU a day.

In Alli’s dosage there is 500 million CFU of reuteri 17938 and 500 million of reuteri ATCC PTA 6475.

There was an effect almost immediately on his allergy; his nose changed colour.  His pollen allergy gets gradually worse in the summer and the sides of his nose becomes bright red.  Short term use of topical steroids reverses this, but the pollen season is four months long.

Along with his red nose, his behavior gets worse leading to aggression,SIB and cognitive decline.  This lasts from mid June to October.  The aggression and SIB responds very well to treatment with Verapamil, but this does not reverse the cognitive decline.  

My behavioural observations might be wishful thinking, but I cannot be imagining bright red fading to a mild pink.

Clearly even at my reduced dosage and lack of the second anti-inflammatory bacteria (L. reuteri ATCC PTA 6475) something very helpful is happening.

As is my habit, I did a quick review of the literature and found plenty of supporting evidence for the potential benefit of specific bacteria on allergy.

As Alli has found, the potential benefit goes far beyond allergy.
  



RESULTS:

Oral treatment with live Lactobacillus reuteri but not Lactobacillus salivarius significantly attenuated the influx of eosinophils to the airway lumen and parenchyma and reduced the levels of tumor necrosis factor, monocyte chemoattractant protein-1, IL-5, and IL-13 in bronchoalveolar lavage fluid of antigen-challenged animals, but there was no change in eotaxin or IL-10. L. reuteri but not L. salivarius also decreased allergen-induced airway hyperresponsiveness. These responses were dependent on Toll-like receptor 9 and were associated with increased activity of indoleamine 2,3-dioxygenase. Killed organisms did not mimic the ability of the live L. reuteri to attenuate inflammation or airway hyperresponsiveness.

CONCLUSION:

Oral treatment with live L. reuteri can attenuate major characteristics of an asthmatic response in a mouse model of allergic airway inflammation. These results suggest that oral treatment with specific live probiotic strains may have therapeutic potential in the treatment of allergic airway disease.


Probiotic Therapy as a Novel Approach for Allergic Disease



Various effects of different probiotic strains in allergic disorders: an update from laboratory and clinical data



The various effects of different probiotic strains in allergic diseases are shown from laboratory and clinical studies referred to in the text.

↑: Increase in symptoms or negative effect; ↓: decrease in symptoms or positive effect; ↔: no change in symptoms or no effect

References
Probiotic strain
Type of allergic disease
Outcome
Atopic dermatitis (eczema)
Sistek et al.[31]
Lctbs rhamnosus + Bfdbm lactis
Food-sensitized atopic children
Kalliomäki et al.[45]
Lactobacillus GG
Atopic dermatitis
Kopp et al.[46]
Lactobacillus GG
Atopic dermatitis
↔, ↑
Wickens et al.[47]
Lctbs rhamnosus
IgE-associated eczema
Viljanen et al.[41,48]
LGG
Atopic eczema/dermatitis syndrome
Rosenfeldt et al.[49]
Lctbs rhamnosus + Lctbs reuteri
Atopic dermatitis
Kuitunen et al.[50]
Lctbs + Bfdbm + propionibacteria
IgE-associated allergy
Boyle et al.[54]
Various
Eczema
Lee et al.[55]
Various
Atopic dermatitis
Soh et al.[63]
Bfdbm longum + Lctbcs rhamnosus
Eczema and atopic sensitization
Food allergy and anaphylaxis
Kim et al.[27]
Lctbs acidophilus + Bfdbm lactis
OVA-induced allergic symptoms
Isolauri et al.[56]
Bfdbm or Lctbs
Food allergy
Majamaa et al.[57]
LGG
Food-sensitized eczema
Shida et al.[60]
VSL#3 + Lctbs casei strain Shirota
Anaphylaxis with food allergy
Hol et al.[61]
Lctbs casei + Bfdbm Bb-12
Cow's milk allergy
Taylor et al.[62]
LGG or Lctbs acidophilus
Cow's milk allergy
↔, ↑
Allergic rhinitis
Di Felice et al.[59]
VSL#3
Allergic rhinitis
Giovannini et al.[67]
Lctbs casei
Allergic rhinitis
Morita et al.[69]
LGG + Lctbs gasseri
Allergic rhinitis
Xiao et al.[71]
Bfdbm longum
Allergic rhinitis; JCP
Tamura et al.[72]
Lctbs casei strain Shirota
Allergic rhinitis; JCP
Asthma
Kruisselbrink et al.[33]
Lctbs plantarum
Dermatophagoides (Der p1) sensitization
Feleszko et al.[43]
Bfdbm-12
Airway reactivity
Blümer et al.[73]
LGG
Allergic asthma
Repa et al.[74]
Lactococcus lactis + Lctbs plantarum
Birch pollen allergen (Bet v1) sensitization
Karimi et al.[75]
Lctbs reuteri
Allergic airway inflammation
Helin et al.[78]
LGG
Pollen allergy


Reader Trials

It would be helpful if readers would share feedback on their use of high dose Biogaia probiotics.

There are many other types of probiotic, but it would be helpful to first focus on the one that has been shown by Alli to be effective.

It seems to me that within a week you are going to know if you have a responder.  As usual you need to see how the effect varies over time.  Numerous interventions seem to be effective and then fade away and some even go from positive to negative.  I will certainly be continuing to see the longer term effect and hopefully finally adding something new to my PolyPill.