I started this post planning to look at diabetes and I had so many hits on microbiome and other autoimmune disease included that I thought that I would move to the full topic.

My word of warning is simple: once the microbiome (gut bacteria) gets shifted out of normal (like with CFS/FM/IBS etc), the odds are significant that the shift could continue to worsen (and depending on you DNA) results in additional and more severe autoimmune diseases.

• “in human male type 2 diabetes subjects as compared to non-diabetic healthy subjects, there were significantly fewer Firmicutes, including Clostridia.
  There were positive correlations between plasma glucose levels and the ratios of Bacteroidetes to Firmicutes, and of the Bacteroides–Prevotella group
  to C. coccoides–E. rectale group. Furthermore, Betaproteobacteria was more abundant in type 2 diabetes subjects than the controls….These results imply that lowered levels of butyrate-producing gut microbes in type 2 diabetes patients may lead to disease pathogenesis” [2017]
• “Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice [2016].
• The gut microbiota: a possible factor influencing systemic lupus erythematosus [2017]. “found a lower Firmicutes/Bacteroidetes ratio in SLE patients vs. controls, there were inconsistencies regarding significant differences in the abundance of specific genera or species. Studies of mouse disease models have shown some correlations between microbial compositions and disease states, also indicating differences between males and females.”
• Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases [2017]
  • A clinical update on the significance of the gut microbiota in systemic autoimmunity[2016].
  • The autoimmunity-oral microbiome connection [2016].
  • Regulation of Autoimmunity by the Microbiome [2016].
• Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology?
• The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs [2017]. “We found that Prevotellaceae were significantly less abundant”
• Correlation of Gut Microbiota Composition with Resistance to Experimental Autoimmune Encephalomyelitis in Rats [2016].
• Altered gut microbiota in RA: implications for treatment [2016]. “Certain gut microbial strains have been shown to inhibit or attenuate immune responses in RA experimental models, suggesting that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of RA.”
  • Lactobacillus salivarius Isolated from Patients with Rheumatoid Arthritis Suppresses Collagen-Induced Arthritis and Increases Treg Frequency in Mice [2016].
  • Probiotic bacteria: a viable adjuvant therapy for relieving symptoms of rheumatoid arthritis[2016].

DNA SNPs

There are some 440+ articles on PubMed finding that some DNA SNPs are associated with diabetes (and other autoimmune conditions). The same appears to apply to almost all autoimmune diseases.

• Polymorphism E23K (rs5219) in the KCNJ11 gene in Euro-Brazilian subjects with type 1 and 2 diabetes [2017].
• PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus [2017].
• Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III [2017].

Other diseases (sample)

• Vitamin D receptor gene polymorphisms are associated with multiple sclerosis in Mexican adults [2017].
• CTLA-4 +49 G/A Polymorphism Confers Autoimmune Disease Risk: An Updated Meta-Analysis [2017].
  • Pathogenic implications for autoimmune mechanisms derived by comparative eQTL analysis of CD4+ versus CD8+ T cells [2017].
• Association of established hypothyroidism-associated genetic variants with Hashimoto’s thyroiditis[2017].
• Polymorphisms of RAD51B are associated with rheumatoid arthritis and erosion in rheumatoid arthritis patients [2017[.
• Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis [2017].
• The association between osteopontin gene polymorphisms, osteopontin expression and sarcoidosis [2017].
• Single nucleotide polymorphisms of IL12B are associated with Takayasu arteritis in Chinese Han population [2017].
• Association of KCNJ2 Genetic Variants with Susceptibility to Thyrotoxic Periodic Paralysis in Patients with Graves’ Disease [2017].
• Association of a single nucleotide polymorphism upstream of ICOS with Japanese autoimmune hepatitis type 1 [2017].
• A Variant in the BACH2 Gene Is Associated With Susceptibility to Autoimmune Addison’s Disease in Humans[2017].
• Estrogen receptor alpha gene ( ESR1) polymorphism can contribute to clinical findings in systemic lupus erythematosus patients[2017].
• Identification of susceptibility gene associated with female primary Sjögren’s syndrome in Han Chinese by genome-wide association study [2016].
• IL-27 Gene Polymorphisms in Iranian Patients with Behcet’s Disease [2016].

Bottom Line

There are several points that I want to make:

• The hope of fixing your DNA is in the remote future at best; the ability to alter your microbiome — while still primitive — exists now.
• The number of DNA SNPs involved and the number of bacteria species and strains are so huge that there is no simple ‘cookbook recipe’. The recipe is to experiment with the “spices and the yogurts in the kitchen” until you find that perfect recipe!

Doing nothing risks moving onto worst autoimmune conditions. Not only worst in terms of symptoms — but also worst in terms of the difficulty to make the microbiome right!

A reader linked me to “Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation [2017]”.

I have mention niacin below in various other contexts:

• Niacin levels in the blood was often low with microbiome dysfunction [2016 Post] and that a precursor (something that converts in niacin) NADH has been shown to help CFS. I wrote “a total absence of studies dealing with Niacin and Chronic Fatigue Syndrome, Irritable bowel disease, Fibromyalgia,” – this has changed…!
• “Is a Niacin Flush an indicator of a specific bacteria (family) in the gut? [2013]“
• E. coli produced Niacin [2012]

The above articles cites:

• “Niacin (nicotinic acid) is also known as vitamin B3 and serves as a precursor for coenzymes such as nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for living cells”
• “One unpleasant side effect caused by niacin is cutaneous flushing. Niacin stimulates prostaglandin D2 (PGD2) release in both mice and humans (Hanson et al, 2010; Song & FitzGerald, 2013), which plays a central role in the niacin-induced flushing. Low-dose aspirin could depress niacin-evoked PGD2 release and reduce the associated flushing (Cefali et al, 2007; Song & FitzGerald, 2013).”
• “In this study, we investigated the therapeutic effect of niacin on colitis both in mice and in patients with moderately active UC. We found that niacin shows anti-inflammatory and anti-apoptotic properties through downregulation of colonic inflammatory cytokine levels, suppression of vascular permeability, and inhibition of colonic epithelium apoptosis by activation of DP1 receptor in macrophages, endothelial cells, and colonic epithelium. Furthermore, treatment with retention enema containing niacin effectively promoted clinical remission and mucosal healing in patients with moderately active UC.”
• “Twenty-six UC patients, who did not respond to conventional therapies, were recruited… Patients were assigned to receive retention enema treatment (including 300 mg niacin/100 ml) daily for 6 weeks … Moreover, 24 out of 26 patients that received niacin treatment underwent overall histological improvement with normal epithelium, mucosal architecture, and lamina propia cellularity and few inflammatory cell infiltration”
• The images below are from the study, and clearly shows improvement!
  
• “Niacin displays multiple beneficial effects on colitis in mice and humans by activation of the PGD2/DP1 axis. These results suggest niacin may become an effective therapeutic option for UC patients.”

Other studies:

• “Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes [2016]” shows the niacin pathways
  
  • “We found that the roles associated with the uptake of the nicotinamide and nicotinic acid  were only present in Actinobacteria, Firmicutes, and a single Proteobacteria…The phyla Actinobacteria and Firmicutes contain lower ratios of de novo producers than the other three, and in these phyla, we observed the presence of the niacin salvage pathways, which are not present in the Fusobacteria and Bacteroidetes genomes.”
  • This study also investigates other B vitamins in depth and recommended reading for CFS researchers.

Bottom Line: Enema Enigmas Again!

In an earlier post, a reader reported very great success from an enemas containing SymbioFlor-1 and Symbioflor-2 (Enterococcus faecalis and E.Coli). The above study indicate benefit from niacin enemas. E.Coli produces niacin — but any association of positive responses may be speculative.

Another 2017 study reports “Collectively, niacin promoted cardiac functional recovery after ischemic myocardial infarction through DP1-mediated M2 polarization and timely resolution of inflammation in hearts.”

Personally, I have taken niacin for the mental clarity that results after a niacin flush. It appears that there were other benefits that are just being discovered!

This is a continuation of my last post looking at other conditions where there is evidence of DNA + Microbiome shift causing a disease. With CFS, the shift has started and may progress into other diseases.

Rheumatoid Arthritis

Microbiome

• “colonization of particular intestinal bacteria was sufficient to induce arthritis.” [2016]
• “A growing number of microbiota constituents such as Prevotella copri, Porphyromonas gingivalis, and Collinsella have been correlated or causally related to rheumatic disease.” [2016]
• “The results of biological research of colon microbiota of patients with rheumatoid arthritis (RA) is in article presented. The signs of III degree dysbiosis, by reducing the concentration of Bacteroides spp., Bifidobacterium spp., Lactobacillus spp. populations, typical strain E. coli. But over growth of populations Klebsiella spp., Proteus spp., Staphylococcus spp., atypical forms of E. coli, Candida spp. The scheme for the correction of the colon microflora of patients with (RA) by was proposed bifiform. Increasing of populations concentration of Bifidobacterium spp., Bacteroides spp., Lactobacillus spp., typical E. coli, Enterococcus spp. and selective decontamination of Enterococcus (Hly+), Klebsiella spp., Proteus spp., Staphylococcus spp., lactosonegative and E.coli (Hly+) confirmed after using of this eubiotics.” [2014]
• Treatment of adjuvant-induced arthritis with the combination of methotrexate and probiotic bacteria Escherichia coli O83 (Colinfant) [2009].
• “Our results indicate that Enterococcus faecium may increase the preventive effect of methotrexate treatment in rat adjuvant arthritis by improving its anti-inflammatory and antiarthritic effects.” [2005]
• ” A growing body of evidence has shed light on the association of dysbiosis of gut microbiota with RA. Certain gut microbial strains have been shown to inhibit or attenuate immune responses in RA experimental models, suggesting that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of RA.” [2016]
• “Patients with RA exhibited decreased gut microbial diversity compared with controls, which correlated with disease duration and autoantibody levels.A taxon-level analysis suggested an expansion of rare taxa, Actinobacteria,…The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A.  A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis.” [2016]
• “A subpopulation of patients with early RA harbored intestinal microbiota dominated by Prevotella copri;” [2016]
• “Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset. With disease development, the abundance of OTUs affiliated with the families Bacteroidaceae, Lachnospiraceae, and S24-7 increased significantly in CIA-susceptible mice….Due to the extreme complexity and diversity of the gut microbiome, it is unlikely that differences in the abundance of a single species are responsible for differences in RA susceptibility. Rather, these differences most likely result from context-dependent interactions among the multiple species constituting the gut microbiota.” [2016]
• “The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.” [2016] [2010]
• “Conclusion: Lactobacillus casei 01 could not improve serum lipids in RA patients.” [2017]
• “probiotics — Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 capsules administered orally.  — did not clinically improve RA as measured by the ACR20,”
• “Subjects who received probiotic capsules – Lactobacillus acidophilus (2 × 10(9) colony-forming units [CFU]/g), Lactobacillus casei (2 × 10(9) CFU/g) and Bifidobacterium bifidum (2 × 10(9) CFU/g) for 8 weeks. —  experienced borderline statistically significant improvement in total- (P = 0.09)” [2016]
• “there were no statistical significant differences in the activity of RA, more subjects in the Lactobacillus rhamnosus GG (LGG) group reported subjective well being.” [2003]

DNA / SNP

• Polymorphisms of RAD51B are associated with rheumatoid arthritis and erosion in rheumatoid arthritis patients [2017].
• Associations between C677T and A1298C polymorphisms of MTHFR and susceptibility to rheumatoid arthritis: a systematic review and meta-analysis [2017].
• Polymorphism and protein expression of MUTYH gene for risk of rheumatoid arthritis [2017].
• Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis [2016].

Bottom Line

The over abundance of Lactobacillus immediately before onset, and no really significant results from any Lactobacillus probiotics strongly suggests that all Lactobacillus probiotics should be avoided.

E.Coli probiotics [Colinfant, Symbioflor-2, Mutaflor] and Bacillus probiotics are what studies suggest are most likely to help. Second line would be: Bifidobacterium spp., Bacteroides spp., Enterococcus spp.

A reader has CFS and also an autistic child. An extension of my model is that DNA + microbiome shift results in a wide variety of difficult to treat conditions falling under autoimmune. This is a drill down into one of these conditions.

Microbiome Shifts

• “Certain intestinal bacteria have been observed in abundance and may be involved in the pathogenesis of ASD; including members of the Clostridium and Sutterella genus” [2017]
• ” At the species level, a relative decrease in abundance of two Bacteroides species and Escherichia coli was found in autistic individuals…. but also may represent a more pervasive dysbiosis that results in metabolites that impact the behavior of autistic children.” [2016]
• “A significant increase in several mucosa-associated Clostridiales was observed in ASD-FGID, whereas marked decreases in Dorea and Blautia, as well as Sutterella, were evident.” [2016]
• “Autistic subjects also harbor statistically significantly (p = 0.015) higher counts of beta2-toxin gene-producing C. perfringens in their gut compared to control children, and the incidence of beta2-toxin gene-producing C. perfringens is significantly higher in autistic subjects compared to control children (p = 0.014). Alpha toxin gene was detected in all C. perfringens strains studied. C. perfringens” [2017]
• “MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).” [2017]
• “unlike those of healthy infants, feces of ASD infants had significantly higher and lower abundance of genera Faecalibacterium and Blautia, respectively.” [2016]
• “from stool samples of children with diagnosed or suspected ASD… Among the species identified, intrinsically fluconazole-resistant Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species..” [2016]
• “Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules)…. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. [2015]
• From a detail study [2015]
  

DNA – SNPs

• “Our findings that WNT2 and FOXP2 may moderate the clinical phenotypes of ASD provide evidence to support the possible universal effect of WNT2 and FOXP2 on neurodevelopmental symptom dimensions.” [2017]
• “A haplotype of WNT2 (rs2896218-rs6950765: G-G) is significantly associated with ASDs in our trios samples,” [2011]
• “Cytogenetic abnormalities at the 15q11-q13 locus are fairly frequent in people with autism, and a “chromosome 15 phenotype” was described in individuals with chromosome 15 duplications. Among other candidate genes are the FOXP2, RAY1/ST7, IMMP2L, and RELN genes at 7q22-q33 and the GABA(A) receptor subunit and UBE3A genes on chromosome 15q11-q13. Variant alleles of the serotonin transporter gene (5-HTT) on 17q11-q12 are more frequent in individuals with autism than in nonautistic populations.” [2004]

BPA – Danger

Interesting that a considerable number of articles returned from the PubMed search reference BPA. ” But BPA lines an estimated 75 percent of canned foods in North America,” [Mother Jones]

• “Short-term feeding of canned dog food increased circulating BPA concentrations in dogs comparable to amounts detected in humans, and greater BPA concentrations were associated with serum chemistry and microbiome changes.” [2017]
• “Gut dysbiosis may result in various diseases, such as metabolic and neurobehavioral disorders. Exposure to endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), especially during development, may also increase the risk for such disorders…., BPA and EE exposure may disrupt the normal gut flora, which may in turn result in systemic effects. ” [2016]

This is a new one on the market that a reader asked me about. It is a single strain: Bifidobacteria bifidum MIMBb75

Going to PubMed to see if there is documentation, I found 8 articles. A good start.

• “Bifidobacterium bifidum MIMBb75 effectively alleviates global IBS and improves IBS symptoms simultaneously with an improvement of quality of life. Considering the high efficacy of MIMBb75 in IBS along with the good side-effect profile, MIMBb75 is a promising candidate for IBS therapy…. Overall responder rates were 57% in the bifidobacteria group but only 21% in the placebo group ” [2011]
• “These findings suggest that probiotic properties of B. bifidum MIMBb75 may partially depend on its ability to at least transiently colonize the intestine and impact on the resident microbial communities at various intestinal loci.” [2013]

Bottom Line

For IBS, I would favor Prescript Assist and Equilibrium as better choices. It is expensive, $50 for 56 capsules.

The Amazon site claims “Only bacteria strain in the world clinically shown to significantly reduce IBS and to simultaneously improve patients’ quality of life.” This is false. They have a 57% response rate, where as Prescript assist “the rate of remissions was 81.5% to 100% (P < 0.003).” [2007]  The studies only show improvement of symptoms, not remission.