In the next 30 to 50 years I think many common diseases will be, in part, treated by bacteria. There is already a great deal of research to show that gut bacteria play a key role in both some diseases and the effectiveness of some therapies.
I was surprised to read that the effectiveness of some common existing cancer drugs appears to depend on the presence, or not, of specific gut bacteria.
Many gut bacteria have very specific, but different, effects on the immune system. There may be no one-size-fits-all options and it is not a case of good bacteria and bad bacteria. Too much of some “good” bacteria and they becomes “bad” bacteria.
Taking a pragmatic approach you can look at the effects of widely available probiotic bacteria and see if any might have a beneficial effect on a specific person’s autism.
We already saw in the trials that people made following Alli from Switzerland’s revelation about the two L.reuteri bacteria found in Biogaia Gastrus, that what is good for one person might not be effective in the next person.
In my case one of the L.reuteri bacteria in Biogaia Gastrus has a profound positive effect on allergy, and hence autism, while the second bacteria has negative behavioral effects. Fortunately, the L.reuteri protectis bacteria in Biogaia Gastrus can be purchased separately.
Not surprisingly, companies are patenting the bacteria with research-proven therapeutic effects. Many supplement companies are using the non-patented bacteria because they are cheaper. Very often they do not specify exactly which sub-type of bacteria they use and you have no means of knowing whether they change the bacteria over time depending on pricing and availability.
Nonetheless if you skim through the probiotic bacteria research and anecdotal evidence there are some interesting options.
First a quick recap
So far in this blog we have seen some particularly interesting individual probiotic bacteria:-
Miyairi 588 from Japan produces butyric acid in the gut. Butyric acid has been shown to have several interesting effects. It improves immune health and for this reason is included in animal feed. It has been shown to improve the integrity of gut to avoid “leaky gut”. It is an HDAC inhibitor which means it may well have epigenetic effects. It is an alternative to using butyrate supplements.
Lactobacillus reuteri 17938 (Lactobacillus reuteri Protectis)
This bacteria is the one we are using and it has potent effects on my son’s summertime allergy that makes his autism much worse.
Lactobacillus reuteri ATCC PTA 6475
This is a potent anti-inflammatory bacteria, but its mode of action does not agree with my son, but it seems to do great things for many others.
Viviomixx and VSL#3
We saw that many people with IBS/IBD and some with autism find these two combination bacteria helpful. Being a mixture of bacteria means that it may be only certain ingredients that have a helpful effect in a specific person with autism.
Many people with types of IBD/IBS do seem to respond well to the combined bacteria found in Viviomixx and VSL#3.
Some other interesting, commercially available, bacteria
I came across several interesting products.
Lactobacillus reuteri NCIMB 30242
This bacteria is very well researched and has effects on some of comorbidities that effect some people with autism, such as vitamin D metabolism and calcium homeostasis.
As is often the case the benefits mainly relate to the immune system. This particular bacteria reduces C-reactive protein (CRP) which is a commonly used marked for inflammation. It reduces “bad” cholesterol and it has an odd effect on vitamin D making it interesting for people with reduced bone density.
I have no idea if it will help some people with autism, but it is very easy to find out since this patented bacteria is available in several products, targeted at your heart, GI or bones but also lightening your wallet.
Given how quick the L.reuteri protectis showed effect (1 day) I only intend to trial NCIMB 30242 for a few days.
Lactobacillus reuteri NCIMB 30242 research
Objectives
The objective of this study was to evaluate the effects of probiotic bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 on cholesterol lowering, mechanism of action and gastrointestinal (GI) symptomatology in hypercholesterolemic adults.
Methods 127 subjects consumed either L. reuteri NCIMB 30242 or placebo capsules over a 9-week intervention period in a randomized controlled trial.
Results L. reuteri NCIMB 30242 capsules reduced LDL-cholesterol by 11.6% (P=0.001), total cholesterol by 9.1%,
Conclusions L. reuteri NCIMB 30242 capsules should be considered as an adjunctive therapy for hypercholesterolemia and may be useful for promoting GI health.
L. reuteri NCIMB 30242 increased serum 25-hydroxyvitamin D by 14.9 nmol/L, or 25.5%, over the intervention period, which was a significant mean change relative to placebo of 17.1 nmol/L, or 22.4%, respectively (P = .003).
CONCLUSIONS:
Building healthy bones takes guts
"We know that inflammation in the gut can cause bone loss, though it's unclear exactly why," said lead author Laura McCabe, a professor in MSU's departments of Physiology and Radiology. "The neat thing we found is that a probiotic can enhance bone density."
In the study, the male mice showed a significant increase in bone density after four weeks of treatment. There was no such effect when the researchers repeated the experiment with female mice, an anomaly they're now investigating.
Lactobacillus Reuteri NCIMB 30350
One reader of this blog is already a fan of Lactobacillus Reuteri NCIMB 30350 which comes from BioAmicus in Canada.
BioAmicus have had feedback from other customers who tried it having read the press reports on Lactobacillus Reuteri and autism.
They told me:-
“The parents who have seen improvement with BioAmicus Reuteri note eye contact, social activity, language use, as well as improved instruction comprehension.”
They plan to make their own autism clinical trial.
Lactobacillus Johnsonii NCIMB 30351
The next interesting bacteria I came across is Lactobacillus Johnsonii. There numerous strains.
This bacteria has been shown to be behind why children who live in a house with pet dog are protected from asthma. Numerous studies like the auto immune disease asthma with increased incidence of autism.
The bacteria is protective against development of another auto immune disease, Type 1 diabetes.
Lactobacillus Johnsonii appears to mediate the effectiveness of some common cancer drugs.
BioAmicus have a Lactobacillus Johnsonii bacteria called NCIMB 30351 usually given to babies.
As some readers have already highlighted Lactobacillus bacteria can be used to make all kinds of yoghurt, kefir etc. So you can grow your own at home to keep the cost down.
Lactobacillus johnsonii research
Early-life exposure to dogs is protective against allergic disease development, and dog ownership is associated with a distinct milieu of house dust microbial exposures. Here, we show that mice exposed to dog-associated house dust are protected against airway allergen challenge. These animals exhibit reduced Th2 cytokine production, fewer activated T cells, and a distinct gut microbiome composition, highly enriched for Lactobacillus johnsonii, which itself can confer airway protection when orally supplemented as a single species. This study supports the possibility that host–environment interactions that govern allergic or infectious airway disease may be mediated, at least in part, by the impact of environmental exposures on the gastrointestinal microbiome composition and, by extension, its impact on the host immune response.
Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of “pathogenic” T helper 17 (pTH17) cells and memory TH1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pTH17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pTH17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.
Although it is known that resident gut flora contribute to immune system function and homeostasis, their role in the progression of the autoimmune disease type 1 diabetes (T1D) is poorly understood. Comparison of stool samples isolated from Bio-Breeding rats, a classic model of T1D, shows that distinct bacterial populations reside in spontaneous Bio-Breeding diabetes-prone (BBDP) and Bio-Breeding diabetes-resistant animals. We have previously shown that the oral transfer of Lactobacillus johnsonii strain N6.2 (LjN6.2) from Bio-Breeding diabetes-resistant to BBDP rodents conferred T1D resistance to BBDP rodents, whereas Lactobacillus reuteri strain TD1 did not. In this study, we show that diabetes resistance in LjN6.2-fed BBDP rodents was correlated to a Th17 cell bias within the mesenteric lymph nodes. The Th17 bias was not observed in the non-gut–draining axillary lymph nodes, suggesting that the Th17 bias was because of immune system interactions with LjN6.2 within the mesenteric lymph node. LjN6.2 interactions with the immune system were observed in the spleens of diabetes-resistant, LjN6.2-fed BBDP rats, as they also possessed a Th17 bias in comparison with control or Lactobacillus reuteri strain TD1–fed rats. Using C57BL/6 mouse in vitro assays, we show that LjN6.2 directly mediated enhanced Th17 differentiation of lymphocytes in the presence of TCR stimulation, which required APCs. Finally, we show that footpad vaccination of NOD mice with LjN6.2-pulsed dendritic cells was sufficient to mediate a Th17 bias in vivo. Together, these data suggest an interesting paradigm whereby T1D induction can be circumvented by gut flora-mediated Th17 differentiation.
Lactobacillus rhamnosus GG
This bacteria has numerous scientifically researched beneficial effects. Most recently it was shown to affect the expression of GABA receptors. For some people with autism this might be beneficial. In particular it may reduce anxiety, since this was the effect noted in mouse research.
Lactobacillus rhamnosus GG (ATCC 53103) is a strain of L. rhamnosus that was isolated in 1983 from the intestinal tract of a healthy human being; filed for patent on 17 April 1985, by Sherwood Gorbach and Barry Goldin, and the 'GG' derives from the first letters of their surnames.
The patent refers to a strain of "L. acidophilus GG" with American Type Culture Collection (ATCC) accession number 53103; later reclassified as a strain of L. rhamnosus. The patent claims the L. rhamnosus GG (ATCC 53103) strain is acid- and bile-stable, has a great avidity for human intestinal mucosal cells, and produces lactic acid. Since the discovery of the L. rhamnosus GG (ATCC 53103) strain, it has been studied extensively on its various health benefits and currently L. rhamnosus GG (ATCC 53103) strain is the world's most studied probiotic bacterium with more than 800 scientific studies.
The patent refers to a strain of "L. acidophilus GG" with American Type Culture Collection (ATCC) accession number 53103; later reclassified as a strain of L. rhamnosus. The patent claims the L. rhamnosus GG (ATCC 53103) strain is acid- and bile-stable, has a great avidity for human intestinal mucosal cells, and produces lactic acid. Since the discovery of the L. rhamnosus GG (ATCC 53103) strain, it has been studied extensively on its various health benefits and currently L. rhamnosus GG (ATCC 53103) strain is the world's most studied probiotic bacterium with more than 800 scientific studies.
The genome sequence of Lactobacillus rhamnosus GG (ATCC 53103) has been decoded.
Medical research and use
While Lactobacillus rhamnosus GG (ATCC 53103) is able to survive the acid and bile of the stomach and intestine, is claimed to colonize the digestive tract, and to balance intestinal microflora, evidence suggests that Lactobacillus rhamnosus is likely a transient inhabitant, and not autochthonous. Regardless, it is considered a probiotic useful for treatment of various maladies, as it works on many levels. Most of the molecular mechanisms are not known, however.
Peanut allergy
Research is showing that L. rhamnosus as a probiotic could stop allergic reactions to peanuts in 80% of children.
Diarrhea
Lactobacillus rhamnosus GG has been shown beneficial in the prevention of rotavirus diarrhea in children. The prevention and treatment of various types of diarrhea has been shown both in children and in adults.
Respiratory tract infections
L. rhamnosus GG may reduce the risk of obtaining respiratory tract infections in children that attend daycare.
Atopic dermatitis, eczema
Lactobacillus rhamnosus GG also has shown potential in treatment and primary prevention of atopic dermatitis, but the results of intervention trials have been mixed. A clinical trial with seven-year follow-up shows L. rhamnosus GG is useful in the prevention of atopic dermatitis in children at high risk of allergy.
Urogenital tract
The clinical health effects of L. rhamnosus GG have been widely studied. Both L. rhamnosus GG and L. rhamnosus GR-1 appear to protect the urogenital tract by excreting biosurfactants to inhibit the adhesion of vaginal and urinary pathogens.
Intestinal tract permeability
L. rhamnosus has been found to reduce intestinal permeability in children who suffer from irritable bowel syndrome, and it also has been found to counter alcohol-related intestinal permeability.
Gastrointestinal carriage of VRE
In 2005, L. rhamnosus GG was first used successfully to treat gastrointestinal carriage of vancomycin-resistant Enterococcus (VRE) in renal patients.
Anxiety
Research published in the Proceedings of the National Academy of Sciences on August 29, 2011 reported this bacterium may have an effect on GABA neurotransmitter receptors. Mice who were fed L. rhamnosus JB-1 had less anxiety and had different levels of a brain-chemical sensor and stress hormones.
This paper was mentioned previously in this blog
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.
Weight loss
Research published in the British Journal of Nutrition in 2013 suggests that Lactobacillus rhamnosus CGMCC 1.3724 may increase weight loss in women who are dieting. The research was initiated after several studies showed that the gut bacteria in obese individuals differs significantly from those in thin people. Women in the study lost nearly twice the weight that the placebo group lost. No difference was observed in men, however.
Risks
The use of L. rhamnosus GG for probiotic therapy has been linked with very rare cases of sepsis in certain risk groups, primarily those with a weakened immune system and infants. Ingestion of L. rhamnosus GG is, nevertheless, considered to be safe, and data from Finland show a significant growth in the consumption of L. rhamnosus GG at the population level has not led to an increase in the number of Lactobacillus bacteraemia cases.
Probiotic Lactobacillus Probiotic rhamnosus downregulates FCER1 and HRH4 expressionin human mast cells
Abstract
AIM: To investigate the effects of four probiotic bacteria and their combination on human mast cell gene expression using microarray analysis.
METHODS: Human peripheral-blood-derived mast cells were stimulated with Lactobacillus rhamnosus (L. rhamnosus) GG (LGG®), L. rhamnosus Lc705 (Lc705), Propionibacterium freudenreichii ssp. shermanii JS (PJS) and Bifidobacterium animalis ssp. lactis Bb12 (Bb12) and their combination for 3 or 24 h, and were subjected to global microarray analysis using an Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array. The gene expression differences between unstimulated and bacteria-stimulated samples were further analyzed with GOrilla Gene Enrichment Analysis and Visualization Tool and MeV Multiexperiment Viewer-tool.
RESULTS: LGG and Lc705 were observed to suppress genes that encoded allergy-related high-affinity IgE receptor subunits α and γ (FCER1A and FCER1G, respectively) and histamine H4 receptor. LGG, Lc705 and the combination of four probiotics had the strongest effect on the expression of genes involved in mast cell immune system regulation, and on several genes that encoded proteins with a pro-inflammatory impact, such as interleukin (IL)-8 and tumour necrosis factor alpha. Also genes that encoded proteins with anti-inflammatory functions, such as IL-10, were upregulated.
CONCLUSION: Certain probiotic bacteria might diminish mast cell allergy-related activation by downregulation of the expression of high-affinity IgE and histamine receptor genes, and by inducing a pro-inflammatory response.
Bifidobacterium Infantis 35624
Bifidobacterium infantis 35624 is marketed in the US by Proctor & Gamble, while in Europe it is sold by the Irish developer.
It is well researched and does have effects beyond the gut.
Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut
Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.
The research highlighted by Proctor & Gamble is here:-
The product is sold as Alflorex in Europe and Align in the US.
Conclusion
One big issue with all probiotics is just how potent they are when you actually consume them, rather than when they are manufactured.
Most people are taking probiotics for very general reasons, but people with IBS/IBD are a group who have very specific problems. VSL#3 and Viviomixx do seem to be the probiotics of choice among those with IBS/IBD.
For allergy and atopic dermatitis some people clearly benefit from specific probiotics such as Bifidobacterium lactis BB-12 and Lactobacillus GG, but not all people respond.
Lowering cholesterol by probiotic is very easy to verify, so I presume it really must work in some cases.
Generally reducing colic, reflux, gas etc. in babies is a claim made for numerous probiotics.
You could spend a vast amount of money on probiotics for autism and it really is only worth using one(s) that have a genuine impact.
It would be useful to collect some data on what dosage is required when somebody actually does respond behaviourally to a probiotic. Thanks to Alli and other readers I think we have the data on Biogaia products.
So far only one reader has given feedback on Lactobacillus Reuteri NCIMB 30350 (Bioamicus), but it was positive. The people at BioAmicus in Canada are very interested to know if their products are effective in some autism.
There are many people in the US using Culturelle for kids with autism, but I did not see any rave reviews. Probably it is used for GI problems rather than to improve autism itself.
It does depend a lot where you live, how easy it is to access specific probiotics at a reasonable price. Some are much cheaper in the US and some cheaper in Europe.
My current list of potentially interesting probiotics is:-
I really never expected to be writing about the merits of probiotics. It was a big surprise to learn that Miyiari 588 is put in animal feed to improve immune health via increasing the SCFA (short chained fatty acid) butyric acid. Butyric acid is relevant to autism. It was a bigger surprise to see L.reuteri Protectis reduce my son’s troublesome pollen allergy and changed the colour of his nose.
It is worthwhile doing some experimentation to see what, if anything, actually is helpful.
There are sound reasons why some people with autism may respond to one of the above bacteria. As of now though, Biogaia is the probiotic of choice to try first, since many people with autism respond well.
All positive and negative feedback on these, or any other probiotic bacteria is very welcome.