A new study on Commercial Probiotics

A few posts ago, I reported

“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!

I then found a site that tests some commercial probiotics for actual Community Forming  Units (CFU). Doing a general search I found this site is helpful for finding CFU in various probiotics: https://labdoor.com/rankings/probiotics 

This morning email found a link to a new study published [Telegraph] [UCL] [PubMed 2015]. I have extracted a table below from this study:

There are several factors that need to be considered looking at studies with the above. We do not need a grain of salt, but we may need a blob of fat!

• If there have been well constructed human studies with the above probiotics with strong results — then that trumps the results of any tests such as those performed above.
• In my prior post(When to take probiotics), we found research that probiotics taken with food or immediately before survived much better than on an empty stomach (a little fat with probiotic is a must IMHO). These tests were done with the “empty stomach” model — the worst case scenario.
• Many studies use animals — in those cases, transit time may be far faster than that seen in humans, resulting in results that may not replicate in humans.
• Diet impact transit times. A high bulk/fiber diet may result in 6+ stool movements a day. Other diets may be just once a day. Thus the results for pig stomach acid may not apply.
• It is unclear is the tests were were ALL of the strains in a multi-strains, or ANY of the strains.

Symprove

Available in UK only. Contains (as ordered on label):

• L. Rhamnosus
• E. Faecium
• L. Plantarum
• L. Acidophilus

Why did it do so well? While they claim (based on beliefs)

• “Critically, Symprove is water-based so it doesn’t trigger digestion, meaning it SURVIVES the hostile environment of your stomach.”
• I believe that the “germinated barley” is the equivalent of “with food”. “Barley is one of the best starchy foods which makes it very suitable for the treatment of problems such as:…” [source]

Bottom Line

For human use, the CFU findings are valid. The results seen were using the empty stomach model which we know maximize the non-survivability of probiotics; a little fat with, and immediately prior to meals are how we know (now) that probiotics should be taken. The results of two L.Casei strains are significantly different — this reinforces that strains are very significant.

So, YES – check out the CFU results on the above sites, in selecting probiotics … and remember to take probiotics with some form of fat (milk, lard, etc).

Update: 2018 Summary on L Reuteri.

This species is used by multiple manufacturers. The 2012 FDA letter (154 pages) is quoted below.

• “L. reuteri NCIMB 30242 may reasonably occur among U.S. consumers seeking foods for the nutritional maintenance of healthy cholesterol levels. L. reuteri NCIMB 30242 will not be added to infant formula, and foods to which L. reuteri NCIMB 30242 will be added will not be marketed for use by infants. “
• “Currently, the strain is manufactured at Chr Hansen (Denmark) using current Good Manufacturing Practices (cGMP). “
• 1.32 to 2.83 10⁸ CFU/g
• “Based on the current long-history of use of L. reuteri in food (i.e., probiotic products, and sourdough bread fermentation), and the fact that the species is natural commensal in many animals including humans, the absence of case-reports of infectivity strongly support that the species can be declared non-pathogenic. “
• “with respect to measures of colonic microflora, other than Bacteroidetes which were increased two- to three-fold in the L. reuteri groups relative to the saline controls, no significant differences between groups were noted.”
• Like the prior L. Reuteri DSM 17938 (BioGaia), this is sensitive to (easily killed by) most antibiotics:
  “genes associated with resistance to fluoroquinolones. These antibiotic resistance elements were demonstrated to be common to other lactobacilli”

• “As reported by Branton et al. (2011) L. reuteri NCIMB 30242 is known to ferment lactose to the above lactic acid mixture in a ratio of 45:55%”i.e. D-Lactic to L-Lactic ratio
• “Lactobacillus reuteri NCIMB 30242 did not display inhibitory activity towards the indicator strains, suggesting that this strain of L. reuteri lacks bacteriocin-like antimicrobial activity. “
• “L. reuteri NCIMB 30242 does not produce measurable quantities of reuterin under these test methods. ” — L. reuteri ATCC 23272  does produce it!
• “The results show a significant decrease in Aspergillus, from baseline, when comparing treatment and placebo groups. All other bacterial (Eubacteria, BacteroidesIPrevotella, LactobacillusIStreptococcuslEnterococcus, Bifidobacterium, Faecalibacteria, Desulfovibrio, Enterobacteria, Clostridium leptum, Clostridium coccoides, Saccharomyces, Candida ) and fungal measurements showed no significant changes between treatment and placebo groups from baseline.”

Bottom Line

The absence of antibiotic production commonly associated with L. Reuteri as well as being sensitive to almost all antibiotics actually makes this strain a poor choice for dealing with dysfunctional microbiome.

Update: 2018 Summary on L Reuteri.

After finding the last FDA report, I thought that a little more digging on the FDA site may be be beneficial to get some behind the scene information. What I found interesting was that it was engineered to be killed by all antibiotics. The “wild”/”original” strain was resistant to some.

I found the 2008 letter dealing with BioGaia’s straws and other uses. The full letter is 118 pages and covers everything you wanted to know about L. Reuteri (as of 2008). Some key points are:

• Strain DSM 17938: aka  ATC 55730, SD 2112, ING 1 and MM 53 are alternative references.
• “are substantially equivalent to their parent strain in all respects other than possession of these plasmids (which contain genes encoding for antibiotic resistance)… did not exhibit tetracycline resistance…, showing complete removal of lincomycin resistance” – in other words, they are less antibiotic resistance than that found in the human gut. Minocycline, doxycycline etc will kill this probiotic off.
• “L reuteri in a drinking straw at the same level. 10⁸ cfu ..The total estimated consumer exposure from these intended uses is less than 10⁹ to 10¹⁰ cfu/day.” – 5 x10⁹ cfu/day is what is reported to be needed to establish a probiotic — that is 50 drinking straws per day.
• “Lactobacillus is a non-pathogenic genus ofLAB that consists of over 112 recognized species as of November 2007 (EFSA 2007).”
• “L reuteri is the only Lactobacillus species reported to inhabit the gastrointestinal tract of all vertebrates and mammals. ranging from birds to humans (Casas and Dobrogosz 2000).L reuteri has been isolated in living form from every part of the digestive tract-the oral cavity. stomach. small intestine. and colon, as well as from stool samples and from the vagina (Reuter 2001).”
• “Overall. 12% oft he mothers had detectable counts of L reuteri in their milk, with a higher rate of incidence in rural than urban areas”
• “The ability of L reuteri to transit the harsh acidic conditions ofthe stomach (with fasting pH of about 1.5 and feeding pH between 3.0 and 5.0) successfully after oral ingestion (Wall et ale 2007) likely contributes to its ability to influence human physiology”
• “Vandenplas et aI. (2007) observed that lactobacilli and other probiotics “do not colonize the gastro-intestinal tract as they become undetectable a few days after stopping the administration. “
• “on animal and human studies of L. Reuteri, a number of animal studies and human clinical trials have established its value in lowering overall pathogen loads and controlling or eradicating infections of Salmonella typhimurium, Enterococcus faecaJis. Cryptosporidium parvum, Helicobacter pylori, and Streptococcus mutans, as well as other microorganisms such as Candida albicans and rotavirus (e.g., Kasravi et al. 1997, Edens et al. 1997, AIak et al. 1999, Balish and Warner 2002, Saggioroa et al. 2005).”
• “L. reuteri, produce both L- and D-Iactate ” (50-50 split)
• “In the presence of glycerol, most strains of L reuteri produce reuterin (3- hydroxypropionaldebyde), a soluble broad-spectrum antimicrobial substance active in a wide range of pH values against Gram-positive and Gram-negative bacteria, especially E. coli, yeasts, fungi, protozoa, and viruses (Cleusix et al. 2007b). Reuterin production occurs during the anaerobic growth of L. reuteri in the presence of glycerol and low concentrations of glucose; it is not clear to what extent reuterin is produced in the human gut…. the production of reuterin was of the same magnitude for the 2 strains.”
• NOTE: Some commercial strains do NOT produce reuterin

Addition Studies

• Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain [2017].
• Oral probiotics in the management of gingivitis in diabetic patients: a double blinded randomized controlled study [2017].
  • “More reduction was present in the test group for Plaque (14%±6) and for Bleeding on Probing ( (18%±4) and was statistically significant (p less than 0.05).  (Lactobacillus Reuteri DSM 17938 and Lactobaciullus Reuteri ATCC PTA 5289) “
• Effect of Lactobacillus reuteri (DSM 17938) on methane production in patients affected by functional constipation: a retrospective study[2017].
  • “a total disappearance of CH4 production (< 5 ppm at LBT) was observed in 11 (of 20) patients,  while, we did not observe any significant decrease of H2 production”
• Probiotic Lactobacillus reuteri has antifungal effects on oral Candida species in vitro[2017].
  • ” exhibited antifungal properties against five of the six most common oral Candida species”
• Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial [2017].
  • “L. reuteri improved insulin sensitivity in a subset of participants “
• Lactobacillus reuteri DSM 17938 plus vitamin D3 as ancillary treatment in allergic children with asthma [2016].
• Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled, cross-over trial [2016].
•  Probiotics for Irritable Bowel Syndrome: Clinical Data in Children[2016].
  • “a treatment for Functional Gastrointestinal Disorders (FGIDs) in children and adolescents concluded that Lactobacillus GG, Lactobacillus reuteri DSM 17938 and VSL#3 significantly increased treatment success.”
• Lactobacillus reuteri DSM 17938 for the Management of Functional Abdominal Pain in Childhood: A Randomized, Double-Blind, Placebo-Controlled Trial [2016].
  • “L reuteri DSM 17938, compared with placebo, significantly reduced the frequency and intensity of FAP in children.”

Bottom Line

L. Reuteri should be taken with glycerol to encourage the production of reuterin (an antimicrobial). This strain has no natural resistance to antibiotics — that was intentionally removed. This suggests that it may not stand up well against dysfunctional bacteria that produces antibiotics/antimicrobials. If you take it, avoid taking it with any other probiotics.

“After a wash-out period of 14 days there was no evidence of either ATCC 55730 or DSM 17938 in the feces of any of the participants.” i.e. it failed to become established or was killed off by other bacteria.

A reader asked for some guidance on selecting Bifidobacteria as a result of a prior post.  Assuming labelling is truthful, I attempted to estimate the cost per CFU (Community Forming Units) below. The minimum goal is at least 5 billion CFU (based on the sparse research available). Five Strain Bifidobacteria came out the clear winner — and most expensive starting cost. Klaire Labs Ther-Biotic Factor 4 is 2nd place with a much lower starting cost.

Formula:   Cost /(Dosages x CFU) i.e. cost / Total CFU in product

Feel free to ping me to compute the numbers for other offerings.

Low levels are associated with other conditions.

For updated information see Microbiome Prescription

DataPunk.Net Data

Very little…

INHIBITED BY

• Bifidobacterium
• Faecalibacterium
• Escherichia

PubMed Data

There are about 17+ articles on PubMed.

• Disease Risks:
  • “Adlercreutzia was also decreased in inflammatory bowel disease  cases compared to controls but was at similar levels in non-responders and responders. ” [2016] Thus high levels suggests reduced risk of evolving to IBD.
  • “control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera. compared to Multiple sclerosis ” [2016] Thus high levels suggests reduced risk of evolving to MS
  • “primary sclerosing cholangitis  was further characterized by decreased abundance of Adlercreutzia equolifaciens” [2017] high levels suggests reduced risk
  • “Colorectal adenoma subjects had … lower abundance of Adlercreutzia compared to controls. ” [2017] high levels suggests reduced risk
• Diet:
  • “Bacteroides spp., Coriobacteriaceae spp. and Adlercreutzia spp. were increased in nonresponders, responders 101, and IBS-D and- M patients, respectively, following a diet low in fermentable carbohydrates( low-FODMAP ).” [2016]
  • “Daidzeins are isoflavonoids commonly found in soybeans that are
    metabolized into the metabolite equol by specific gut microbes, such as the aptly named Actinobacteria species,” [2016] [2012]
  • “Adlercreutzia and Lactobacillus which were found to be enriched in Low Fat” [2016] compared to ” high-fat (40 E% saturated fat, HF) control diet, or heat-treated high-fat (200 °C for 10 min, HT) diet, for 8 weeks.”
• Prebiotics:
  • “In contrast, Adlercreutzia, Odoribacter, and Coprococcus were significantly more abundant in microcrystalline cellulose group M,”
• Probiotics:
  • ” there was significantly lower … Adlercreutzia equolifaciens following both interventions( the L. casei Zhang or vitamin K2 ) compared to the model group. ” [2017]
  • “a fermented dairy product (FDP) fortified with Bifidobacterium animalis subsp. lactis… Increased lactose fermenting taxa included Slackia isoflavoniconvertens and Adlercreutzia equolifaciens; ” [2017]
• Antibiotics:
  • “Ten OTUs indicating fluoroquinolone treatment were associated with Blautia, Subdoligranulum, Adlercreutzia, Clostridium and Ruminococcus.” [2014]

Bottom Line

• Do not do a low-FODMAP diet
• No soy (it’s a food source)
• Vitamin K2 supplementation
• Lactobacillus Casei probiotics
• E.Coli Probiotics (Mutaflor, Symbioflor-2)
• No Bifidobacterium animalis subsp. lactis probiotics
• No fluoroquinolone antibiotics