In a recent post on dry mouth as well as an earlier post, I emphasis that the mouth can often be a reserve for dysfunctional bacteria that may repopulate the gut. Beyond traditional good mouth hygiene (water pick, brushing, hydrogen peroxide mouth rinse), the use of oral probiotics should be consider to dislodge existing bacteria. These should usually be taken after the above hygiene.

There are many oral probiotics out there today. I have extracted a table, shown below, with the species as well as the cost per billion Community Forming Units (B-CFU). The cost varies greatly from a low of 8 cents per B-CFU to a high of $5.50 — ouch!

Oral Probiotics are marketed for one purpose, reduce cavities. We are actually doing an “off-label” usage – altering the mouth microbiome. This means that we actually want multi-species oral probiotics and not single strains that are cavity specific (K12, M18, JH145).

I would recommend the following two as starters.

• Swanson Oral Probiotic
• PRO-Dental: Probiotics for Oral & Dental Health 3

Why?

• Price
• But more critical, both contain L.Reuteri and no  L. Acidophilus
  • The absence or low level of L.Reuteri is associated with many symptoms seen in CFS

Remember, the dosage on the package is for normal healthy individuals — I usually do double that dosage for therapeutic.

Side Note/Pleasant Surprise: While doing Christmas stuff, I nicked a finger and was pleasantly surprised that it bleed easily (profusely may be a better description) despite not having taken any anti-coagulants for a week. This could be interpreted as suggesting that at least some coagulation factors are significantly impacted by the microbiome/probiotics.

This is my periodic review of recent news dealing with probiotics.

• “Any two humans typically differ by about 1 in 1,000 DNA bases, whereas bacteria of the same species may differ by as many as 250 in 1,000, Snyder said. “I don’t think people realized just how much diversity there was. The complexity we found was astounding,” he said….”For example, many strains of E. coli bacteria live harmlessly and even helpfully in the human gut, while others are lethal. Being able to tell one strain from another could help researchers determine which strains are dangerous and why.” [2015] – Reinforces the need to work at the strain level.
• “Resistant starch (RS) type 2 is present in cereals, tubers, legumes, and fruits [4]. In animal models, consumption of RS improves gut integrity and absorption of nutrients and reduces T cell infiltration of the mucosa [5–7]. In humans, the consumption of RS changes the composition of the microbiota and promotes the microbial fermentative production of short-chain fatty acids (SCFA), which putatively reduce gastrointestinal inflammation [8–10]. RS also improves symptoms and reduces pathology in inflammatory bowel disease [11]. In addition, RS meets the criteria for safety, durability, and availability as a dietary intervention to reduce environmental enteric dysfunction (Subclinical, chronic gut inflammation) EED.”[2015]
• “effects were lasting, since the overall recovery of the microbial mass, bacterial diversity and concentrations were still below pre-antibiotic values 4 months after the end of antibiotic treatment.” [2015]
• Lactobacullus plantarum 299V increases iron uptake [2015] This STRAIN is available from Jarrow and is sold on Amazon.
• “Increased intakes of fermented foods like kimchi and beer are associated with significantly reduced risks of atopic dermatitis (eczema), says a new study from Korea… 44% lower prevalence…” [2015]
• “The potential for the gut microbiota to affect health has a particular relevance for older individuals. This is because the microbiota may modulate aging-related changes in innate immunity, sarcopaenia, and cognitive function, all of which are elements of frailty. Both cell culture–dependent and –independent studies show that the gut microbiota of older people differs from that of younger adults. There is no chronological threshold or age at which the composition of the microbiota suddenly alters; rather, changes occur gradually with time. Our detailed analyses have separated the microbiota into groups associated with age, long-term residential care, habitual diet, and degree of retention of a core microbiome. We are beginning to understand how these groups change with aging and how they relate to clinical phenotypes. These data provide a framework for analyzing microbiota-health associations, distinguishing correlation from causation, identifying microbiota interaction with physiological aging processes, and developing microbiota-based health surveillance for older adults.” [2015]
• “Overall, the present study emphasizes the need to disentangle gut microbiota signatures of specific human diseases from those of medication.”[2015] – i.e. not controlling for medications being taken can result in suspect results.
• “The researchers observed that commensal E. coli are no longer proliferating 20 minutes after an animal eats, and that the bacteria produce a different suite of proteins than during mealtimes. Giving these proteins to rodents caused the release of peptide YY, which signals fullness, and caused the animals to eat less.”[2015]
• “Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet….the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.” [2015]
• “we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals.” [2015]

The picture below summarized the last item — the “goodness” or “badness” of a food is very individual and gut bacteria is a significant factor.

Intestinal permeability (“leaky gut”) is another leading factor in the development and progression of non-alcoholic fatty liver disease [2014], which gives us a condition to also search on.

A 2015 study found “Antitumor necrosis factor-α(TNF-α) therapy reduces mucosal inflammation and restores intestinal permeability in IBD patients. Butyrate, zinc, and some probiotics also ameliorate mucosal barrier dysfunction but their use is still limited and further studies are needed before considering permeability manipulation as a therapeutic target in IBD.” and continues with:

• “To date the ones with proven efficacy are Escherichia coli Nissle 1917, Bifidobacterium,Lactobacillus rhamnosus GG, or the multispecies VSL#3 which contains eight different probiotics [132]”
• “Zinc is a trace element essential for cell turnover and repair systems. Inflammatory conditions and malnutrition are known risk factors for zinc deficiency and several works proved the efficacy of its supplementation during acute diarrhoea and experimental colitis [127–129]”
• “Finally, vitamin D is worth a mention because it is involved in maintaining intestinal barrier function”
• “Furthermore, there is increasing concern about the role of industrial food additives as promoters of immune-related diseases. A recent review showed the ability of additives to increase intestinal permeability by interfering with the TJs, promoting the passage of immunogenic antigens [113].”

Wait a minute — these seem to be the same items that I recommended for CFS!

• “A butyrate-producing probiotic (MIYAIRI 588) reduced the lipid deposition and significantly improved the triglyceride content, IR, serum endotoxin levels, and hepatic inflammatory indexes in a rat model of choline-deficient diet-induced Non-alcoholic fatty liver disease[77].” [2014] This is Miyarisan!
• “In particular,Lactobacillus casei DN-114001[60] and VSL#3 (a mixture of pre- and probiotics)[61] seem to restore intestinal barrier function by enhancing the expression of ZO-2 and protein kinase C in TJs. … Escherichia coli strain Nissle 1917 restored mucosal permeability in the murine dextran sulfate sodium-induced colitis model by increasing ZO-1 expression[43].” [2014]
• “Bifidobacterium longum was superior in attenuating liver fat accumulation… lack of changes in intestinal permeability in treated mice” [2014]
• “With regard to exercise-induced GI permeability problems, there is still a lack of studies with appropriate data and a gap to understand the underlying mechanisms”[2012] – this may be a significant factor for the CFS crash after exercising, increased leaky gut!
  • “..cycling resulted in increased I-FABP levels, reflecting small intestinal injury … This is the first study to reveal that ibuprofen aggravates exercise-induced small intestinal injury and induces gut barrier dysfunction in healthy individuals. We conclude that nonsteroidal anti-inflammatory drugs consumption by athletes is not harmless and should be discouraged.” [2012]
  • “Exercise-induced splanchnic hypoperfusion results in quantifiable small intestinal injury. Importantly, the extent of intestinal injury correlates with transiently increased small intestinal permeability, indicating gut barrier dysfunction in healthy individuals.”[2011]

Short List of What to take

• Probiotics
  • Miyarisan (Clostridium butyricum) – Available in US, UK and Japan (note that it also reduces Anxiety in CFS by 50%)
  • Mutaflor (E.Coli Nissle 1917) – Available in Germany, Canada, Australia
  • Bifidobacterium – which includes Align and others,
  • Lactobacillus rhamnosus GG – Culturelle
  • VSL#3 aka Vivomixx
• Zinc
• Vitamin D3 – likely 15000 IU in many cases
• Butyrate

Avoid PREPARED foods, food from raw materials is strongly preferred.

An Alzheimer connection?

An Oct 2015 article “Different Brain Regions are Infected with Fungi in Alzheimer’s Disease” suggests that leaky gut may be a contributing factor for AD.

“Many investigators have also considered the idea that AD is an infectious disease, or at least that infectious agents constitute a risk factor for AD^21,22,23. Accordingly, genetic material from several viruses and bacteria have been reported in brains from AD patients. In particular, herpes simplex type 1 (HSV-1) and Chlamydophila pneumoniae have been suggested as potential aetiological agents of AD. In addition, brain infection by several pathogens may induce amyloid formation^24,25,26. Furthermore, Αβ peptide exhibits antimicrobial activity and shows particularly strong inhibitory activity against Candida albicans²⁷.”

This appears to be further indicated by this earlier 2015 study “Increased concentrations of fecal calprotectin indicate a disturbed intestinal barrier function in AD patients which could be of relevance for the lowering of essential aromatic amino acids concentrations in the blood.”

Interesting that IBD and IBS are different here “Fecal calprotectin has been shown to consistently differentiate IBD from irritable bowel syndrome because it has excellent negative predictive value in ruling out IBD in undiagnosed, symptomatic patients.” [2006]

If you have IBS — you may wish to have fecal calprotectin tested to verify if it is IBD or IBS (and potentially if you have a higher Alzheimer’s Disease risk).

A light went on?

Hypoperfusion (decrease access to tissue) produces increased leaky gut. Hypocoagulation produces hypoperfusion. Hypercoagulation(aka “Thick Blood”) has been reported to occur in over 85% of CFS patients (not severe enough to cause strokes, some may have TIAs). Is hypercoagulation why there may be significant increase in leaky gut in CFS after exercise (see earlier post). That is — there was already significant hypoperfusion before exercising resulting in an amplified response with exercise?

There appear to be some studies heading in that direction….

• Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinalinflammation [2011].
• Effects of coagulation factor XIII on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation in experimental endotoxemia [2006].

Recently I was asked what probiotics to take when you have a Vitamin D defect (a VDR genetic mutation). In answering this, I referenced the reader to: “Vitamin D receptor pathway is required for probiotic protection in colitis.” [2015] which reports:

• “We found that the probiotics Lactobacillus rhamnosus strain GG (LGG) and Lactobacillus plantarum (LP) increased VDR protein expression in both mouse and human intestinal epithelial cells.”

The first one is our long time friend, Culturelle (available on Amazon and also at Costco often). For the second one, I discovered that Swanson now has a single species version

I noticed that there were additional single species probiotics from Swanson. I have summarized in a table below