Yakult – L.Casei Shirota

I have frequently cited this probiotic but have not done an actual post on it. I Today I discovered FDA documentation on it which I have extracted below.

  • “Additionally, L. casei ferments lactic acid from many other precursors. Only the L-enantiomer of lactic acid is formed.” so no d-lactic acid 🙂
  • “L. casei strain Shirota is 100 percent identical to those of L. casei strains designated ATCC 334 and NCDO 151.”
  • “L. casei strain Shirota, like most lactobacilli, is resistant to vancomycin; however, this resistance is not genetically based.”
  • “Yakult describes L. casei strain Shirota as a non-pathogenic and non-toxigenic bacterium.”
  • “ingredient in fermented dairy products at a maximum level of 4×108 colony forming units (cfu) per milliliter (ml).”
  • “The notifier states thatL. casei strain Shirota up to 3.6×1011 cfu/day fed to healthy adults for as long as 5 weeks and to health-compromised adults up to 8×1011 cfu/day for as long as four years, showed no adverse effects.” i.e. 2 liters of Yakult/day

From the alternative names listed above (there are 200+ citations for casei shirota), I found that

  • it produces a”class IId bacteriocin that exhibited antimicrobial activity against some lactobacilli and several Listeria species.”[2013]
  • “cultivation of Lactobacillus casei ATCC 334 in the presence of human intestinal epithelial cells promotes functional changes in bacteria. In particular, the interaction enhanced the immunosuppressive phenotype of L. casei as demonstrated by the ability of L. casei to generate functional regulatory T cells (CD4+CD25+FoxP3+) and production of the anti-inflammatory cytokine interleukin-10 by human peripheral blood mononuclear cells.” [2013]

Impact on CFS:

  • “Decrease in Anxiety symptoms Increase in Lactobacillus and Bifidobacteria in Fecal samples”[2015] [2009]

It is not effective for IBS but will mitigate some symptoms  (and by inference, only symptom mitigation for CFS) – i.e. reduces inflammation:

  • “After probiotic treatment with LcS, no improvement of 30% in MSS was observed after 8 weeks.” [2016]
  • “Some trials showed a significant improvement of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota” [2005]
  • “There was no significant improvement in the symptom score with probiotic therapy, except for wind (P = 0.04).” [2008]

Similarly, for UC, its impact is again reducing inflammation:

  • “This probiotic-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines such as IL-6 and IFN-gamma production in LPMC. Therefore, LcS may be a useful probiotic for the treatment of human inflammatory bowel disease.” [2005]
  • “probiotic strain Lactobacillus casei Shirota in UC partially restored their normal function indicated by reduced Toll-like receptor 2/4 expression and restoration of their ability to imprint homing molecules on T cells and to generate interleukin-22 production by stimulated T cells.” [2014]

Bottom Line

Yakult has a role in reducing inflammation and potentially to displace some dysfunctional bacteria. It will likely reduce some symptoms.

 

Parasites, Microbiome and CFS

A common refrain in CFS research is that in a sample of CFS patients, 10X of the patients have infection Y and in a control group only X has infection Y. The “Y” may be EBV, Q-Fever, Positive Chronic Lyme tests, or parasites. This is done by researchers trying to identify the cause of CFS using simplistic logic.

To me, the simplest way to KISS these findings is that they are consequences of the CFS state. A reader forwarded me a study “Probiotics for the Control of Parasites: An Overview” [2011] which actually (indirectly) explains why some CFSers have a high incidence of parasites.

Before going into that, let us revisit viral infections (such as EBV, HHV6 etc), many/most are never eliminated, rather your immune system learns to keep them in control. The classic example is the zoster virus which produces chicken pox.

“After you get better from chickenpox, the virus “sleeps” (is dormant) in your nerve roots. In some people, it stays dormant forever. In others, the virus “wakes up” when disease, stress, or aging weakens the immune system. Some medicines may trigger the virus to wake up and cause a shingles rash. It is not clear why this happens. But after the virus becomes active again, it can only cause shingles, not chickenpox.” [WebMd]

We find that “Human populations are infected with 8 herpesviruses, including herpes simplex virus HSV1 and HSV2 (also termed HHV1 and HHV2), varicella zoster virus (VZV or HHV3), EBV (HHV4), cytomegalovirus (HHV5), HHV6, HHV7, and Kaposi sarcoma-associated herpesvirus (termed KSV or HHV8).” [2013] – note that almost all of these have been associated with CFS (i.e. over-represented in CFS patients compared to controls).

We know that CFS patients are low in B12 and that L.Reuteri is the bacteria that produces B12 in healthy people. L. Reuteri is very low in CFS patients . This means they are no protected against these parasites by L.Reuteri which is in abundance with healthy mammals.

Surprise, surprise, surprise! L.Reuteri results in 75+% reduction of many parasites/pathogens including [2011]:

L.Casei also results in similar reduction of:

You may being say — what! How can this be! The article does a nice explanation of what probiotics do, namely:

“Modulation of the intestinal environment, by probiotics having the capacity to control the proliferation of surrounding microorganisms and/or by competition for the occupancy of a common biotope (e.g., access to nutriments) [2]. For example, iron is a limiting nutriment: it is essential for most bacteria, and probiotics can compete for its availability. Lactobacillus can render iron unavailable for pathogenic microorganisms, either by binding ferric hydroxide on its surface [4] or by secreting siderophores that chelate and transport iron [3].” So if you are low in Iron, a lactobacillus probiotic may not be ideal.

“Secretion of active molecules (e.g. bacteriocins, antibiotics, free fatty acids, hydrogen peroxide) that can control growth and/or survival of surrounding microorganisms. Bacteriocins are secreted peptides or proteins that generally kill closely related bacteria by permeabilizing their membranes or by interfering with essential enzymes (…. Lactobacillus reuteri produces reuterin (3-hydroxypropionaldehyde), a broad-spectrum antibiotic, active against bacteria, yeast, fungi, protozoa, and viruses [7]. By lowering the local intestinal pH with lactic acid, probiotics can also modify the growth of acid-sensitive organisms [5].”

A second article, “The Unexplored Role of Probiotics on the Parasitic Pathogens. Food and Nutrition Sciences [2014]” reports

“Recent evidences gathered from in vitro culture systems or at best in animal models have demonstrated that probiotic bacteria can be used for therapeutic purposes on control of both intestinal parasite infections as well as few non-gut infections spread among human and veterinary animals. ” and further adds this important finding

“The good effects of probiotics is largely dependent on the dose ingested of at least five billion colony forming units per day for at least 5 days [2009] which acts as a minimum dose for the survival capacity of the ingested probiotics in the gastrointestinal system to overcome the competition with the resident bacteria.” Note: This is 5 billion of a specific species — not grand total of many species!

  • “Also, serum of L. casei-treated mice has shown 1.8 (app.) times more nitric oxide concentration which provides a protective effect upon the plasmodial infection. “

Bottom Line

L Reuteri and L. Casei are important probiotics to address parasites. They are also both on my recommend list (being the exceptions to avoiding any random Lactobabillus probiotic — just like Mutaflor(E.Coli Nissle 1917) is the exception for any random E.Coli).

A second take-away is that you want your dosage to be at least 5 billion of a specific species and to take it for 5 days. Any less dosage and it will be a flow thru probiotic that has temporary effect only.

Consider the probiotic below:

61-xqydm-1l-_sy679_

We have just 1.5 billion a day — no way near enough. And there are three species — so an average of 0.5 billion a day of each species… oops… what will NOT happen?  (oh,yes — I get it, you will have to keep buying this probiotic!!!) these probiotics will NOT get established.

To quote from an European Probiotic researcher that I have corresponded with “you are outside of the spectrum, because the cfu/g is too low.”

For Miyarisan (Clostridium butyricum) tablets, we read that there is about 10 million viable bacteria per tablet [food.gov.uk] so a full recommended dosage of 18 x 10 million, takes you up to 180 million only.

The research on the needed dosage and duration to establish a probiotic is sparse. There are financial incentive to not release such data (because keeping below that dosage results in constantly repeating customers for the product). The dosage reported above seems “high” but just a few years ago, 400 IU of vitamin D a day seemed very high (and today, 15,000 IU is known to be safe and of great benefit for diabetes, cancer and CFS symptoms).

“While there are no established Upper Limits for probiotic intake, various clinical studies have noted that doses up to 15 billion CFUs of beneficial bacteria have shown efficacy in the maintenance of digestive health/reversing occasional irregularities and doses up to 450 billion CFUs have shown efficacy in the treatment or symptomatic relief of Irritable Bowel Syndrome (IBS).” [Source]

Doing a general search I see that almost every one is keeping below this threshold for any species or have a complex mixture. This site is helpful for finding out tested cfu, https://labdoor.com/rankings/probiotics 

  • Exception: Culturelle : Single Species 14 Billion CFU [Source]
  • Yakult: Single Species 8 Billion asserted

Align was tested to be only 160 million CFU [Source] which means 40 capsule a day to get up to 5 billion.

The rest are BLENDS — Lactobaccillus being in significant quantities. My concern is that different probiotics may compete with each other resulting in less effective CFU (or randomness of which one is the winner!). The same two species (B.lactis and L.Acid.) appear to be the “filler” in many of the mixures.

“The recent publication of the PROPATRIA study (Besselink et ale 2008), which reports higher mortality among subjects with acute pancreatitis treated with a combination of 6 strains of live Lactobacillus and Bifidobacterium species has caused some to question the safety of probiotics. “[Source]

  • Healthy Origins® Probiotic 30 Billion CFU’s is a powerful blend of 8 friendly bacteria strains and 30 billion colony forming units (cfu’s) ==> with Bifidobacterium (animalis) lactis and L. acidophilus being above the 5 billion cfu threshold.
  • ULTRA-30 Probiotics 30 Billion CFU’s & 18 Strains Supplement ==>
  • This one provides two above the desired level, ExtraFlora 50 Billion CFU Probiotics,  — one of which is Bifidobacterium (animalis) lactis
    51pkxhctxil

“Over the past 30 years there have been about 180 published cases of bacteremia and 69 cases of endocarditis putatively caused by lactobacilli (Aguirre and Collins, 1993; Gasser, 1994; Donohue and Salminen, 1996).” [Source]

 

 

Commercial Bifidobacteria probiotics

In my last post, we found that low Bifidobacteria was common across many illness/syndromes deemed to be in the autoimmune family. We also found that Lactobacillus increases as Bifidobacteria increases – in other words they are complementary and cross supporting, with the key observation that Lactobacillus increases inflammation while Bifidobacteria decreases it. This may account for the poor/non success of Lactobacillus probiotics for CFS.

A good list of probiotics available is at CandidaDiet showing various combinations and their alleged content. Alleged? That’s the sad news.

Strains are rarely listed and Contents may not be as advertised!

“A new study by scientists at the University of California has found that contents of many bifidobacteria probiotic products differ from the ingredients listed….16 products.. only one matched the ingredient list .. Some products also contained non-label species” [Source 2015] –OUCH!

Studies

Criteria: Studies with only Bifidobacteria probiotics. (There is a probiotic, BIO-THREE, which does not have Bifidobacteria but it does cause an increase according to PubMed [2007] – I have made inquiries with the manufacturer on retail availability in the US)

Probiotic Conditions Study
Bifidobacteria infantis 35624 CFS,ulcerative colitis, Psoriasis reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions[2013]
Bifidobacterium breve strain Yakult ulcerative colitis improve the clinical condition of patients with UC [2011]
Bifidobacterium enterococcus; Bifidobacterium lactobacillus (Bifico) ulcerative colitis is effective in preventing flare-ups of chronic UC. [2003]
Bifidobacterium longum Y 10, B. infantis Y 1 and B. breve Y 8 (VSL-3) colitis, crohn’s, IBS, Many StudiesMany Studies “evidence for the use of probiotics in IBD is scarce. Most studies are limited by design or do not show that probiotic treatment is effective. Only a few randomised controlled trials have demonstrated any beneficial effect of probiotic use in IBD; namely, the use of VSL#3 in patients with pouchitis and ulcerative colitis.” [2012]
Bifidobacterium breve strain Yakult, Bifidobacterium bifidum strain Yakult ulcerative colitis has anti-inflammatory effects against ulcerative colitis. [2008]

Apart of VSL-3, there are almost no clinical trials against various conditions. The Japanese Probiotic company, Yakult, appears to be a dominant player in this area.

So, we know that low levels are associated with many conditions, we know that what is labelled on the bottle may not be what is in the bottle, almost no-one give strains, there are few clinical studies…  Welcome to the art of probiotics. 😦

I have assembled a table of species and commercial products below for at least some guidance.  In general, I would not advocate anything containing L. Acidophilus.

Screen Shot 2015-11-26 at 11.42.27 AM

Rules of thumb:

  • Select the one with the most B. Species at a reasonable cost (i.e. Monthly Cost/Species)
  • Change probiotics when you finished a bottle.
  • Try getting different species each time you change

— Key words from above chart/image

NOW Foods Acidophilus/bifidus ProBiota Bifido Life Extension Bifido GI Balance Align Natren Bifido Factor Dairy Free Flora Baby Klaire Labs Ther-Biotic Factor 4 Nestle Beba ProNature Made Digestive Probiotics Advance Dual Support Active Balance High Potency Probiotic Bayer TruBiotics CVS Digestive Probiotics Pearls Elite Florajen 3 Kyo-Dophilus Good FloraLife Start 2 Nature Made Triple Probiotic Nature’s Way Primadophilus Intensive Philips Colon Health Probioplus DDS Five Strain

  • Bifidobacterium animalis
  • Bifidobacterium bifidum
  • Bifidobacterium breve
  • Bifidobacterium infantis
  • Bifidobacterium lactis
  • Bifidobacterium longum

 

Bifidobacteria role in multiple diseases and gluten allergies

In my last post there was an interesting items on Bifidobacteria that I want to dig into:

“Bifidobacteria are common and frequently dominant members of the gut microbiota of many animals, including mammals and insects. Carbohydrates are considered key carbon sources for the gut microbiota, imposing strong selective pressure on the complex microbial consortium of the gut. Despite its importance, the genetic traits that facilitate carbohydrate utilization by gut microbiota members are still poorly characterized. Here, genome analyses of 47 representative Bifidobacterium (sub)species revealed the genes predicted to be required for the degradation and internalization of a wide range of carbohydrates, outnumbering those found in many other gut microbiota members.” [2015]

Crohn’s Disease[CD] have problems with starches/carbohydrates, and we find:

“Lactobacillus and Bifidobacteria decreased obviously but Bacteroid increased in CD patients” [2010]

“except for a decrease in bifidobacteria in the active state of IBD,”[2010]

“among the few bacterial groups considered, only bifidobacteria were significantly decreased in IBS samples.” [2014]

“Rifaximin, a rifamycin derivative, has been reported to induce clinical remission of active Crohn’s disease (CD)…it caused an increase in concentration of Bifidobacterium, Atopobium and Faecalibacterium prausnitzii.” [2010]

“with lower levels of bifidobacteria, celiac patients have an imbalance in the intestinal microbiota” [2014]

“In comparison to patients with fibromyalgia, the RA patients had significantly less bifidobacteria”[2008] – NOTE: there was no comparison to controls in this study.

Treatment Results – Suggestions

“We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the Lactobacillus casei strain Shirota(Yakult) , and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01).” [2009]

“Live probiotic Bifidobacterium lactis bacteria inhibit the toxic effects induced by wheat gliadin in epithelial cell culture” [2008 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453197/)%5D

From Intestinal Microbiota and Probiotics in Celiac Disease, 2014 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135898/)

“Bifidobacterium infantis 35624 alleviates symptoms in IBS; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a pro-inflammatory cytokine, suggesting an immune-modulating role for this organism, in this disorder.”[2005 (http://www.ncbi.nlm.nih.gov/pubmed/15765388)%5D

“a probiotic dietary supplement, containing four strains of lactic acid bacteria, on symptoms of IBS.. the probiotic combination was not significantly superior to the placebo in relieving symptoms of IBS” [2008 ] Note: Bifido works, Lacto does NOT.

“Bifidobacterium strains are generally regarded as less pro-inflammatory than Lactobacillus,” [2008 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640389/)%5D

“There were statistically significant difference in expansion of bacteria between the wholemeal and white flour (wholemeal more bifidobacteria, white more lactobacillus) (p = 0.02; p = 0.04, respectively).”[2014 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065312/)%5D – so avoid food using white flour

“gum arabic has prebiotic effects to increase bifidobacteria in the human body (13 14  [2014]

Which Probiotics?

“It has been demonstrated that levels of bifidobacteria and lactobacilli are reduced in CD patients, and thus, these bacteria have been seen as promising targets for probiotic therapy. However, there is still a lack of consensus regarding the shifts in bacterial composition, primarily at the species level. Thus, future studies should emphasize microbiota characterization with potential benefits to gut health. Strains capable of producing enzymes that degrade gliadin peptides and induce anti- inflammatory effects are believed to be better suited for the treatment of this disorder.” Intestinal Microbiota and Probiotics in Celiac Disease, 2014

My next post will look at commercial probiotics that are mainly bifidobacteria.

Probiotics News 2015-11-24

“Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink” [2015]  This STRAIN is available from Jarrow and is sold on Amazon.

“Eating a bowl of porridge oats a day could alter gut microbial functions, according to Scandinavian researchers who have tipped the ingredient as a possible prebiotic.”[2015]

“People with better control of blood sugar after eating barley kernel bread also have a different balance of microbes in the gut, a new study in Cell Metabolism reveals..Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after BKB” [2015]

“Low counts of a bacterial species generally have been discounted in importance, but slight shifts in the ratios of abundant microbe populations have been thought to have roles in obesity, diabetes and inflammatory bowel diseases such as Crohn’s disease.”[2015]

“Supplements containing Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, andBifidobacterium longum MM2 may shift the microbiota of elderly adults to those of healthier and younger people, says a new study”[2015]

“Diagram showing how various species gut bacteria matches other species:” [Source]

111415_scivis_inline_730

“Intestinal worms manipulate their host’s immune system to ensure their survival, in part by changing the metabolism of the host’s gut microbiome. The worms, called helminths, infect around 2 billion people around the world, and are able to block harmful inflammatory responses in humans and mice.” [2015]

“Bifidobacteria are common and frequently dominant members of the gut microbiota of many animals, including mammals and insects. Carbohydrates are considered key carbon sources for the gut microbiota, imposing strong selective pressure on the complex microbial consortium of the gut. Despite its importance, the genetic traits that facilitate carbohydrate utilization by gut microbiota members are still poorly characterized. Here, genome analyses of 47 representative Bifidobacterium (sub)species revealed the genes predicted to be required for the degradation and internalization of a wide range of carbohydrates, outnumbering those found in many other gut microbiota members.” [2015] NOTE: Bifidobacteria are often very low with CFS — which implies carbothydrates are not handle, possibly leading to gluten and other issues with starch.

“Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation”[2015]