Thursday, 15 November 2018

Probiotics/Prebiotics – Very good for Some, but no Panacea

This is another post that I had waiting for completion; it is not saying do not use pre/probiotics, it is just saying make sure you know what you are doing.  Plenty of people appear to be wasting their money on ineffective bacteria, some people are making themselves sick, but others get a genuine benefit worth paying for. The is no one-size fits all. Some bacteria are good for some people and bad for others.

It gets more expensive the further you live
from Switzerland, but with the right oral 
bacteria you need a very modest amount.

One of today’s studies shows that spending money on stool tests for bacteria to fine tune a therapy may be a waste of money, unless you do your homework first. 

There is currently a lot written about the role of the gut microbiome on human health. Unfortunately, it tends to get simplified into just good bacteria and bad bacteria.  Advice like “take a good bacteria” is not very useful.

The reality is that some people take a store-bought pre/probiotic bacterium and it does nothing, for some it makes them feel worse and for others it makes them feel better.

It is rather like taking a random drug from the pharmacy and hoping for the best. In the case of autism, it is clear that some people make their child’s life worse with these pills, while sometimes it makes them better.

The idea of custom-made personalized probiotics sounds interesting, but it assumes that the bacteria found in a stool sample is representative of what is living in different parts of your intestines. Unfortunately, a recent study in humans that took samples from different parts along the intestines and compared the result with a non-invasive stool sample, found that the results did not correlate. In other words, drawing too many conclusions from the bacteria found in stool samples is unwise. This challenges the business case for   custom-made personalized probiotics.Modifying bacteria in your body has huge therapeutic potential for some people, but the science is still in its infancy. There are also promising results from fecal transplants (Bacteriotherapy), which is another way to modify the gut microbiome.

“As of 2013, fecal transplantation is currently not routinely performed for indications other than recurrent C. difficile colitis. More research studies are still needed to determine if fecal transplantation should be performed for other clinical indications. Fecal transplantation for other clinical indications should be considered experimental, and performed only as part of a research study where your safety is closely monitored.”

"Although all of our probiotic-­consuming volunteers showed probiotics in their stool, only some of them showed them in their gut, which is where they need to be," co-author Eran Segal from Weizmann added. "If some people resist and only some people permit them, the benefits of the standard probiotics we all take can't be as universal as we once thought.

A group of scientists in Israel claim foods that are packed with good bacteria - called probiotics - are almost useless.
Their study is among the most detailed analyses of what happens when we consume probiotics.
They are seen as healthy and good for the gut, but the results found they had little or no effect inside the body.
The researchers said probiotics of the future would need tailoring to the needs of each individual.
The team at the Weizmann Institute of Science made their own probiotic cocktail using 11 common good bacteria including strains of Lactobacillus and Bifidobacteria.
It was given to 25 healthy volunteers for a month.
They were then sedated and samples were surgically taken from multiple places in the stomach and small and large intestines.
The researchers were looking to see where bacteria successfully colonised and whether they led to any changes in the activity of the gut.
The results in the journal Cell, showed in half of cases the good bacteria went in the mouth and straight out the other end.



  • The murine & human gut mucosal microbiome only partially correlates with stool
  • Mice feature an indigenous-microbiome driven colonization resistance to probiotics
  • Humans feature a person-specific gut mucosal colonization resistance to probiotics
  • Probiotic colonization is predictable by pre-treatment microbiome & host features
Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.

In this work, we profiled the homeostatic mucosal, luminal, and fecal microbiome along the entirety of the gastrointestinal tract of mice and humans. We demonstrated that solely relying on stool sampling as a proxy of mucosal GI composition and function may yield limited conclusions.
Our results highlight several important concepts. First, we expand the scope of description of the human microbiome bio-geographical compositional and functional landscape, and indicate that extrapolation from stool microbiome communities to those of specific GI mucosal and luminal niches may lead, in some cases, to inaccurate conclusions. By directly comparing the stool and mucosal presence of 11 probiotic strains of the most commonly used probiotic genera, we conclude that probiotic strain expansion in stool, highlighted by most previous studies to be a sign of probiotics efficacy, cannot distinguish between true probiotic-permissive and resistant individuals, in which probiotics in stool represent a transient ‘‘washout’’ of non-colonizing strains passing throughout the GI lumen without significantly adhering to the host mucosal layer.

Second, the marked and person-specific mucosal colonization resistance to probiotics noted in our study may explain the high variability in probiotics effects on the host or its microbiome noted in previous works. One important feature shown in our studies to play a central role in impacting individualized probiotic mucosal colonization is the indigenous gut microbiome, which may drive the observed person-, strain-, and region-specific colonization resistance patterns to probiotics, as previously suggested. Similarly, we have recently demonstrated that person-specific variations in microbiome composition and function may contribute to the variability in glycemic responses to a variety of foods

Finally, the identified baseline microbial and host factors potentially enabling prediction of a probiotics-permissive or -resistant state merit validation in larger cohorts and call for consideration of a transition from anempiric ‘‘one size fits all’’ probiotics regimen design, to one which is based on the consumer. Such a measurement-based approach would enable integration of person-specific features in tailoring particular probiotics interventions for a particular person at differing clinical contexts.

Probiotics can cause SIBO (small intestine bacterial overgrowth)

In the recent study below, it is suggested that probiotic use can lead to small intestine bacterial overgrowth (SIBO) and the elevated levels of D-lactic acid in blood, then leads to “brain fogginess”. Stopping taking the probiotic (and taking an antibiotic) pretty much solves the problem.

We describe a syndrome of Brain Fogginess (BF), gas and bloating, possibly related to probiotic use, SIBO, and D-lactic acidosis in a cohort without short bowel. Patients with BF exhibited higher prevalence of SIBO and D-lactic acidosis. Symptoms improved with antibiotics and stopping probiotics. Clinicians should recognize and treat this condition.

Bacteria to calibrate the immune system

We saw in earlier posts that the bacteria the fetus and baby are exposed to are used to calibrate the future immune response, which is then pretty much fixed for life. During evolution humans have developed expecting to be exposed to certain bacteria, that today we might regard as just dirt. By living in an ultra-clean environment, we are doing the next generation no favours.

Exposure to bacteria from pets and farmyard animals is very healthy, but only when this is done during pregnancy and shortly thereafter. Once the child’s immune system has been programmed to expect almost no bacteria it is maladapted to cope with future allergens and challenges to the immune system. The result is it over-reacts and produces eczema, asthma, food allergies and many other auto-immune diseases.    

An example showing the benefit of applying knowledge of bacteria

At the risk of digression, here is an example of truly beneficial oral bacteria.

Some years ago, in this blog I reviewed the evidence that drinking beetroot juice boosts exercise endurance and lowers blood pressure.  I was intrigued by this idea, since it is a really simple, healthy and it is easy to measure your blood pressure. Beetroot is rich in nitrates (NO3-) and your body coverts these to nitrites (NO2-) and then later on it uses an enzyme called eNOS (endothelial nitric oxide synthase) to produce nitric oxide in your blood vessels. This dilates them (opens them up) and lets more blood through. This allows endurance cyclists, or marathon runners, to keep going longer and for couch potatoes it lowers their blood pressure. People with vascular conditions like vascular dementia should also benefit from more NO, they may lack the enzyme eNOS if they are elderly. We saw this is my post on Arginine, which suggests that older adults should be taking ALA or NAC, rather than blood pressure reducing meds.

Arginine and its Derivatives in Cognitive Impairment

the progressive impairment in endothelium-dependent vasodilation is caused by a progressive alteration of the L-arginine-NO pathwayOnly in old age (after ≈60 years) does the production of oxidative stress appear, leading to the complete compromise of NO availability.  

For the scientist among you, things are actually much more complex.

Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis

“Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function.”

For the rest of us, basically, we are cheating to improve vascular NO homeostasis. Nitrates are present in other food like spinach and kale, foods many people would avoid, just as would beetroot.

I did an experiment to see if a modest dose (200ml) of beetroot juice would reduce my own blood pressure; it did and by more than a trivial amount. So, I thought I would actually continue with it.

Having now done all my homework I have got the blood pressure benefit from just 80ml of beetroot juice a day, along with an understanding of the bacteria in my mouth that converts the nitrate into nitrite. This means I can reduce my beetroot consumption by more than half to a non-bothersome amount.

Any kind of mouthwash will kill the bacteria needed to make nitrite (NO2-), as will toothpaste. Unless you really want to drink a large glass of beetroot juice every day, you just take 80 ml of beetroot juice and slowly swirl it around in you mouth to react with the bacteria that has been multiplying overnight, before you brush your teeth in the morning.

I finally found a 100% beetroot juice that actually tastes pleasant. It is Swiss and so at least it is consistently the same, unlike the others I tried which ended up being more apple juice than beetroot juice or just tasting vile.

The advantages of an 80ml beetroot juice “mouth rinse”: -

·        Lower systolic blood pressure by about 10 mmHG
·        Lower LDL cholesterol, via the flavonoids
·        The betanin (the red colour) protects against Alzheimer’s in animal models
·        Likely has other (neuro) vascular benefits, perhaps including reducing vascular dementia
The bacteria science, as an example of what you can figure out from publicly available sources: -


The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human body. NO is, at present, recognized as a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalysed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO3--NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalysed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.

The role of salivary glands and oral bacteria in the NO3--NO2--NO pathway. Up to 25% of the circulating nitrate is actively taken up by the salivary glands and concentrated 10- to 20-fold in the saliva to maintain the enterosalivary circulation of NO3--NO2--NO. This key process is mediated by sialin, which is an electrogenic NO3-/H+ transporter in the plasma membrane of salivary acinar cells. When saliva nitrate is secreted into the oral cavity with dietary nitrate—which is reduced to nitrite by the commensal facultative anaerobic bacteria at the posterior aspect of the tongue—some of the nitrite is converted into NO at the stomach. However, most of the remaining nitrate and nitrite are absorbed in the intestine and directly enter the systemic circulation, generating NO in blood and tissues under physiologic hypoxia and playing biological effects.

Role of Oral Bacteria on Nitrate Reduction to Nitrite
Humans, unlike prokaryotes, are believed to lack the enzymatic machinery to reduce nitrate back to nitrite. However, due to the commensal bacteria that reside within the human body, it has been demonstrated that these bacteria can reduce nitrate, thereby providing an alternative source of nitrite. Bacteria are vital in the process of converting nitrate to nitrite—the crucial first step in the NO3--NO2--NO pathway.

Location of Nitrate-Reducing Bacteria in the Mouth
After an oral nitrate loading, gastric NO concentration increases continually. The importance of oral bacteria in gastric NO generation has been clearly illustrated in experiments using germ-free sterile rats, in which gastric NO formation is negligible even after a dietary load of nitrate. The experiment also showed that NO is very low in rats treated topically with an antiseptic mouthwash.
Interestingly, the gastroprotective effects of dietary nitrate, discussed in the section below, virtually disappeared in rats treated with antiseptic mouthwash solutions. The posterior surface of the tongue is responsible for the majority of nitrate reduction, while in the entire oral cavity the nitrate reduction is found to vary widely among individuals. Studies on rats have also shown that nitrate reductase activity occurs on the posterior surface of the tongue and that significantly higher proportions of gram-negative bacteria were found deep within the tongue clefts as compared with the surface.

Composition of Nitrate-Reducing Bacteria

The major nitrate-reducing bacteria can be classified into 2 broad categories—the strict anaerobes (Veillonella atypica and Veillonella dispar) and the facultative anaerobes (Actinomyces odontolyticus and Rothia mucilaginosa;). The facultative anaerobe A. odontolyticus also displays markedly greater ability to reduce nitrate following incubation under anaerobic conditions. However, it is the strict anaerobes (Veillonella spp.) that have been found to be the most prevalent nitrate reducers on the tongue and therefore may be a major contributor to nitrate reduction in the oral cavity. Recently, by using 16S rRNA gene pyrosequencing and whole genome
shotgun sequencing and analysis, scientists have found a higher abundance of Prevotella, Neisseria, and Haemophilus than Actinomyces on the posterior surface of the tongue.

Saliva Nitrate Protecting against Gastric Damage

Nitrate secreted from the salivary glands is found to have an unprecedented function in protecting against stress-induced gastric damage. A water immersion–restraint stress assay in rats shows decreased blood flow in gastric mucosa and induced hemorrhagic erosions after bilateral parotid and submandibular duct ligature. In animals that had received either cardiac ligation or oral treatment with povidone-iodine, a potent bactericidal agent, administration of nitrate failed to increase gastric levels of NO and to inhibit the mucosal injury. NO that is formed close to the gastric mucosa can easily diffuse through the mucosa to the submucosal arterioles, causing vasodilatation and thus increasing gastric mucosal blood flow. This process protects gastric epithelial cells from necrosis. In addition, the decrease of mucosal myeloperoxidase activity and the expression of induced NO synthase with nitrate pretreatment imply that nitrate can reduce tissue inflammation, making this mechanism a possible way of gastric protection. In the absence of a dietary nitrate intake, salivary nitrate originates mainly from NO synthase. Thus, oxidized NO from the endothelium and elsewhere is recycled to regulate gastric mucus homeostasis.


There are some very clever things that can be done by modifying the bacteria in your gut, but if you get it wrong you can very easily make things worse. In some cases, people create a problem where non-existed.

Taking probiotics is not so different to taking drugs, care is needed.

You cannot just produce a general list of good bacteria and bad bacteria. The effects of some bacteria are very specific, and an ever so slightly different variant of one bacterium can do something completely different. Also, what is a good bacterium for one person can be a bad bacterium for the next person.

If you go back to when there was a lot of discussion in this blog about probiotics, this pretty much fits in with the comments. A few people had a good result, some people had a horrific experience and for many there was no effect, except on their wallet.
Many supplements actually contain a relatively tiny number of bacteria and by the time you consume them, you have no idea how many are still alive.

Growing your own bacteria gets around the potency problem, once you have found one that actually gives a benefit.

I do think there is great promise to treat a small number of people by transplanting the microbiome of a healthy person. Only a small number of people are going to need this.

The safest way to “improve” your microbiome is through eating a healthy varied diet, with fruits, vegetables and fiber, which many people resist doing.

Regular exposure to pets and their dust/dirt during pregnancy is on my list of how to minimize future autism. Pets are also calming which should lower oxidative stress and of course dogs make you go for long walks.

For late middle-aged people and older, beetroot juice really is a good intervention and for the really committed add a glass of natural yoghurt with teaspoon of turmeric and high flavanol cocoa (if you can find it), otherwise it is rather expensive Cocoavia from Mars. The yoghurt increases the bioavailability of the turmeric ten times, apparently. 


  1. Hi Peter and community,

    This is another great post, and in fact useful for me as my blood pressure is borderline, so I'm going to test the "Beetroot Juice mouthwash" protocol to see if it makes an impact.

    Also, for the community, I found the following fascinating article on imaging results potentially upending a current ASD theory which you may find of interest:

    An item I found of particular interest towards the end was the following: " If these initial conclusions are confirmed, it would make it possible to consider the development of new therapeutic approaches for deficits in social cognition. For example, transcranial magnetic stimulation could be explored because brain connectivity between adjacent areas is located on the surface of the brain."

    Finally, the following recent paper on NCAM1 caught my eye and I just wanted to share:

    Have a great evening everyone!


    1. AJ - I am lucky to have an appointment with a research neurologist on monday who is using TMS. Will present him with several papers and ask him to be my daughters ‘personal’ research neurologist. Will let you know what he says. Tyler: while I am not an autism study with 1000s of people in it, I surely talked to hundreds of autism parents so far. The gist is - GFCF brings minor barely there improvements, diets like SCD or GAPS or for some Nemechek (inulin) bring major improvements. That sort of jibes with that you say.

    2. Hi Tatjana,

      That's great news! Getting to work with researchers who can provide access to tools that aren't easy for parents to access is a huge benefit.

      I have my fingers crossed for you that he / she will agree to be your "personal" research neurologist.

      It would be wonderful to hear back from you on any unique testing / treatment (such as TMS) you pursue and how it goes.

      Tatjana, without having to name the gene, have you had a genetic mutation identified (and have you had genetic testing)?


    3. We did a maximized genetics test with advanced mthfr panel. We didnt do 23andme for reasons of technical problems (filling the vial) and privacy (Labcorp is...well, what it is). She has comt and mao stuff. I am currently in the process of getting a consult with someone over the mutations because recently I have stopped getting into everything myself because there is sp many things now. As we speak, I am doing this, the neurologist, sending a mitoswab tomorrow, awaiting the genetic consult so we can put in a good detox supplementation so we can start DMSA, i just found someone to make me the right clonazepam dosage and I am trying to find a schedule for fecal transplants in Bratislava.

    4. Hi Tatjana,

      That's great, you are clearly on top of things and being very proactive. Your child is lucky to have such a dedicated mom.

      The reason I asked is that you are working to find a "personal" neurologist, and I can tell you from personal experience, that the best thing I ever did was to reach out to researchers who are working on my daughter's specific gene. I am working with two incredible research teams and for any parents out there who have either not done a genetic test, or have not done a very thorough one, I would so highly recommend that they do this so that they know the relevant gene (assuming one can be found) so that they can connect with research teams working on that gene.

      From personal experience, the one that we did was the following, but as Peter will tell you, there are benefits and drawbacks to any test, so I am only listing this as I liked the facts that (1) they looked at ~2,500 genes and (2) they compared mom and dad's 2,500 genes to the child's to see if the mutation was novel:

      It's expensive, but it really worked for us.

      Ideally, once we know which gene(s) is the likely culprit, we can "map" out the affected pathway and compare this to the normal pathway to identify what goes wrong as a result of the mutation.

      I wish you the best of luck Tatjana on all that you are doing, and I look forward to hearing how you do, especially with the TMS. Hopefully you see some good improvement.


    5. What were the concrete results you got? I mean effects of the counseling and subsequent therapeutic approaches?

    6. Hi Tatjana,

      The relevant gene (which I haven't noted publicly) is a gene that hasn't been fully investigated, so there wasn't much counseling to do per se, but I reached out to the 3 research teams working on the gene, and all 3 kindly responded to me.

      The main team is running iPS / mouse studies to learn more about how mutations in the gene affect individuals, while the second team I am working with is running mouse models (not iPS yet). The protein products of my gene (there are multiple proteins from this gene due to alternative splicing) are still mysterious, and their interactions with other proteins are not fully understood yet. As soon as we have a better understanding of the normal and affected pathways, we will see what interventions may be applicable / available.

      The third team has been superficially helpful, but I don't believe they are pursuing this gene as proactively as the other two, likely due to budgets, so I don't expect anything from team 3.

      So as for now, I am waiting to hear about results from teams 1 and 2. Both teams have been great.

      I also recently started very productive conversations with an incredible team that isn't focused on my gene specifically, but neurodevelopmental disorders in general, and I am very likely to work with them as well. In fact, there are some really exciting possibilities here that I am pursuing that I will likely provide details on in the future.

      So all in all, until I have a better understanding of the affected pathway, I'm in a holding pattern, but once I do have a better understanding of the underlying pathway resulting from the relevant mutation, I will have a far better idea of how to address the issue. I'm confident next year will be a big year in this regard.


    7. Tatjana,
      I second AJ here, since we also were "lucky" to get a hit with DNA testing with my daughter.

      While there aren't any official therapies for her syndrome yet, the genetic result has given me things like:
      -Contact with a research team interested in the gene
      -Relevant scientific papers to read, from which I learned about hypofunctioning NMDArs and a lot of other stuff
      -A small community where I can ask what other interventions have already been tried, and what issues I'll have to look out for in the future. Actually, I have even tried to set up a community driven trial of krill oil + buttermilk after AJ found a paper mentioning this intervention associated with my daughters gene. While I still don't know if it works, I have learned tons of things on why it could work in this condition.


    8. Hi AJ,

      I guess it was WES/WGS that revealed that rare and not fully investigated gene variant in your daughter (?). Could you share if your daughter was offered that test because of autism or any other coexistent condition or symptoms?

      So few children have such tests done and I wonder what would be the best approach to this kind of genetic testing in autism with/without additional issues.

      It is really great to hear about your cooperation with the research teams and hopefully your daughter will benefit from their work soon.

    9. Hi Agnieszka,

      So we were actually offered a free test a couple of years ago from the physician who made the diagnosis (I assume it was via our provincial health system), but we said no to it as it required a blood sample (a vial or two) and as my daughter is so afraid of anything medical that I couldn't imagine putting her through that at that young age. So I searched and found that GeneDx did their test using cheek swabs, so I went with them. I paid for it personally (~$3,500 US) so it was more me that drove this particular test than it being offered (although one was offered for free but I chose not to do it due to it requiring a blood draw).

      The test we did targeted ~2,500 known ASD / ID related genes, so it was neither whole genome nor whole exome, but the exomes of 2,500 candidate ASD / ID genes.

      You make such a wonderful point about so few children having done such tests, because prior to this test, I didn't know if our issues were due to gut microbiome, environmental toxins, genetic issues, and now I know what it is.

      To every reader of this blog who has not yet done a genetic test, I would say this is the most important first step I would recommend. If you do get a "Hit", it opens up many many new doors.

      There are pros and cons to various tests, including the one I did. We are actually going to be doing a WGS shortly to ensure that we haven't missed anything, and that one is a blood draw …

      Thank you kindly for your words about my daughter. We are getting much closer to finding out what the affected biological pathways are due to the researchers and once we know that, we will be much closer to finding ways to benefit my daughter.

      I hope this is helpful Agnieszka!


    10. Hi AJ and thank you for explaining it all.

      If you think about long term autism costs in general, then genetic tests of this kind do not seem so expensive and indeed may contribute to the treatment now or in the future.

      I found that the least stressful way for blood draws for both my children is at home and straight after they wake up, acutually when they are still in beds. There is a lab here which offers at home blood draw service and while I previously had general concerns about any medical procedure to be done at home, it proved to be the most easy-going. And just got the positive feedback from another parent who arranged the same for her child with autism who resisted blood draws in the past.

      AJ, would you mind sending me a contact email to you via the address published here in Peter's blog on the Verapamil for Autism page? I would appreciate if I could ask you one more thing, also a general question, but rather for the email type of conversation.

      Again, thanks for sharing the details, it is very helpful.

  2. Somewhat tangential to this post, a new study suggests self-reported benefits of a gluten-free diet, including reduced intestinal bloating, has little to do with the gluten itself, but rather the composition of the dietary fiber you tend to get from a gluten free diet, rather than from the type of fiber you get from high gluten foods like wheat and rye.

    Press Release:


    This is interesting because several large quality autism studies have been done on the GFCF diet and found it to be bunk, yet you still have plenty of anecdotal reports that never seem to die from parents talking about how the GFCF diet has helped their child. Much of it I still believe is due to various biases on the part of the parents, but perhaps some or even many of these anecdotal reports have a grain of truth in them (no pun intended) in that getting more fiber from cruciferous plants, as opposed to grains, may benefit some people with microbiomes that don't like grain fiber for whatever reason.

    1. Interesting Tyler,
      I seem to do very bad with eating bread and cereal like products, Since around 2-3 years ago I have completely removed them from my diet and eating outdoors for lunch and taking a sandwich often reflects in acne like symptoms for 3-4 days after aswell as headache like symptoms.
      I seem to do well on quinoa and couscous as main carbohydrate sources

  3. Since we are on the subject of probiotics/nitrates I thought Id add the following, considering my past experience with GPLC (glycine propionyl-l-carnitine). As the name might sound like propionic (aka propionic acid aka bad news), it seems to actually be the oposite for GPLC! In fact it seems protective.

    Let me just say I have a hard time comprehensing how this works, but the GPLC form of carnitine would seem the most promising one:

    Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature.

    Regression of fibrosis/cirrhosis by Glycine propionyl-l-carnitine treatment in d-Galactosamine induced chronic liver damage

    Glycine propionyl-L-carnitine modulates lipid peroxidation and nitric oxide in human subjects.

    Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males

    Glycine propionyl l-carnitine attenuates d-Galactosamine induced fulminant hepatic failure in wistar rats.

    Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

    Propionyl-L-carnitine: biochemical significance and possible role in cardiac metabolism.

    "Propionyl-L-carnitine traverses both mitochondrial and cell membranes. Within the cell, this mobility helps to maintain the mitochondrial acyl-CoA/CoA ratio. When this ratio is increased, as in carnitine deficiency states, deleterious consequences ensue, which include deficient metabolism of fatty acids and urea synthesis. From outside the cell (in blood plasma), propionyl-L-carnitine can either be excreted in the urine or redistributed by entering other tissues. This process apparently occurs-without prior hydrolysis and reformation. It is suggested that heart tissue utilizes such exogenous propionyl-L-carnitine to stimulate the tricarboxylic acid cycle (via succinate synthesis) and that this may explain its known protective effect against ischemia."

    Ok dont really full understand it, but seems to influence urea to some extend which would explain my positive reaction.

    Contrasting effects of propionate and propionyl-L-carnitine on energy-linked processes in ischemic hearts.

    "In the postischemic phase, contractile parameters were partially restored both in the control and in the propionate plus carnitine-treated hearts, were markedly impaired by propionate, and were fully recovered by propionyl-L-carnitine. In addition, propionyl-L-carnitine, but not propionate, reduced the functional decay of mitochondria prepared from the ischemic hearts. Even in normoxic conditions propionate, unlike propionyl-L-carnitine, caused a drastic reduction of free CoA and L-carnitine. The concomitant increase in lactate production and decrease in ATP content might be explained by the inhibition of pyruvate dehydrogenase caused by the accumulation of propionyl-CoA. Indeed, when pyruvate was the only oxidizable substrate, propionate induced a gradual decrease in developed pressure, which was largely prevented by L-carnitine. The protective effect of propionyl-L-carnitine may be a consequence of the anaplerotic utilization of propionate in the presence of an optimal amount of ATP and free L-carnitine."


  4. Propionyl-L-carnitine as potential protective agent against adriamycin-induced impairment of fatty acid beta-oxidation in isolated heart mitochondria.

    "Addition of PLC to ADR-incubated myocytes induced 79% reversal of ADR-induced inhibition of palmitate oxidation. In isolated rat heart mitochondria, ADR produced concentration-dependent inhibition of both palmitoyl-CoA and palmitoyl-carnitine oxidation, while PLC caused a more than 2.5-fold increase in both substrates. Preincubation of mitochondria with 5 mM PLC caused complete reversal of ADR-induced inhibition in the oxidation of both substrates. Also ADR induced concentration-dependent inhibition of CPT I which is parallel to the inhibition of its substrate palmitoyl-CoA. In rat heart slices, ADR induced a significant (65%) decrease in adenosine triphosphate (ATP) and this effect is reduced to 17% only by PLC. Results of this study revealed that ADR induced its cardiotoxicity by inhibition of CPT I and beta-oxidation of long-chain fatty acids with the consequent depletion of ATP in cardiac tissues, and that PLC can be used as a protective agent against ADR-induced cardiotoxicity."

    Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases.

    "No side effects were reported during treatment or at 4 wk follow-up visit."

    PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD (crohn) patients."

    Reversal of cisplatin-induced carnitine deficiency and energy starvation by propionyl-L-carnitine in rat kidney tissues.

    Just wow, Ive looked inside the study and it completely normalizes BUN and creatine kinase back to control group.

    Also pretty remarkable to actually see it helps the gut rather than be very bad for it such as with propionic acid.

  5. Very interesting paper for everyone that uses probiotics:

    Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions

    Really worth a read and a look at the graphs

  6. Can anyone explain why BDNF on its own downregulates KCC2 but when you add a TrKB inhibitor like curcumin or genistein, BDNF upregulates KCC2?
    I guess this is the reason you do curcumin Peter(?)


    1. Ling, it is very complicated and very poorly described in the literature.

      The effect of BDNF and TrkB activation on KCC2 expression does appear contradictory. Some of this relates to whether you are looking at immature (epileptic/autistic) neurons or mature neurons.

      Here is a very recent paper with very good illustrations, if you can access the full text. It makes it clear that much is not understood.

      Seizing Control of KCC2: A New Therapeutic Target for Epilepsy

      I would simplify the science into the case we are interested in which is the immature neuron (autistic or epileptic) which I think takes us to.

      TRKB activation downregulates KCC2
      BDNF decreases KCC2 expression

      Numerous studies have noted that BDNF is elevated in autism and at least one found a correlation between autism severity and the BDNF level.

      The effects of curcumin on BDNF and TrkB are also contradictory and in different circumstances the effect is the opposite. Curcumin can increase BDNF in diabetes but reduce it in some cancer.

      I think at a dose large enough to get absorbed Curcumin will have a positive effect in some autism. I do not know whether it will help shift immature neurons towards mature by increasing KCC2 expression.

      I am not regularly giving curcumin to Monty, but I did just start giving it to myself in the bioavailability-boosting form of 1 teaspoon mixed in a small glass of regular fat plain yogurt. After 2-3 weeks I am going to do some lab tests.

    2. Yes, obviously very complicated and confusing with the contradictory pathways in mature vs immature neurons.
      Thanks for sharing your knowledge on this! :-)
      And I hope those lab test have something to tell you.


  7. Peter et al,
    Replenishing certain gut bacteria reverses social deficits in several mouse models of autism from Neuron (read about it in the Spectrum Report) "Interestingly, the effects of L. reuteri on social behavior are not mediated by restoring the composition of the host’s gut microbiome, which is altered in all of these ASD models. Instead, L. reuteri acts in a vagus nerve-dependent manner and rescues social interaction-induced synaptic plasticity in the ventral tegmental area of ASD mice, but not in oxytocin receptor-deficient mice. Collectively, treatment with L. reuteri emerges as promising non-invasive microbial-based avenue to combat ASD-related social dysfunction." Could someone explain how it helps in the vagus nerve....?. And how would you know what you child be responsive to-- the oxytocin receptor deficient etc? Thank you! MH

    1. MH, in earlier posts we saw that certain L.reuteri bacteria cause oxytocin to be released, but we did not know how this happened. It turns out that it is already known that some types of vagus nerve stimulation also lead to oxytocin being released. The recent research just connects the two; the mechanism behind the benefit of L-reuteri involves a stimmulatory effect on the vagus nerve. The commercial products that seem to produce oxytocin include Biogaia Protectis and Bioamicus.

      My son becomes more emotional when taking Biogaia Protectis, it is obvious that his behaviour changes. He is already quite friendly, so he does not need it.

      If someone is very socially withdrawn, they might well benefit from taking the right L.reuteri probiotic.

    2. Peter I cant find anything on protectis (L. reuteri DSM 17938) having an effect on oxytocin release, all the studies done that show the oxytocin boosting effect seem to use atcc 6475 and this is only present in biogaia gastrus atm.

      However from what I understand is that DSM 17938 and ATCC 6475 even have oposing effects, dsm 17938 seems to enhance tnf-a/il-6 where as atcc 6475 does the oposite.

      I find it interesting however as my 23andme data shows I have a very rare gene that leads to LESS il-6, its extremely interesting since most herbs/supplements Ive seen to respond to actually lower il-6. Makes me wonder how much of the biogaia gastrus im trying is actually due to atcc 6475, pherhaps DSM 17938 is also having an effect on me.

      Once I close to running out of biogaia gastrus ill make an order of gastrus + protectis and will start very very low on protectis, since I have crohn genes and I might have either a very positive or very bad response to protectis.


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