Toward a Personalized Approach in Prebiotics Research

A particularly timely commentary was published last week in the Nutrients Journal. It was published “open access” under a Creative Commons license, so feel free to read, share, and quote appropriately.

Dr. Moul Dey, professor at South Dakota State University has been studying resistant starch and human health. She’s noticed variations between people when they supplement with different types of RS, just as we have. Dr. Dey’s commentary gives some very poignant insight to the inter-personal variations and the ramifications of individuality in treating diseases of the gut.

Please read the entire commentary, it’s not too long. I had thought about copying and pasting it here, since it would be legal under the license, but instead I decided to just pull my favorite lines.

From:   Toward a Personalized Approach in Prebiotics Research (Dey, 2017)

Mapping microbiome diversity has unlocked many mysteries—but also triggered new questions. The answers to many such questions still elude us, including a very basic but pressing question, “what diet is ideal for a healthy gut microbiome?” It remains unknown if there is an ideal gut microbiome that can be considered “healthy”, nor do we know of one ideal diet that can positively manipulate the microbiome of people of all ages across the globe. Furthermore, a plethora of contradictory research findings on what dietary component may or may not be healthy frequently confuse the public.

Scientists prioritize collective outcomes with high statistical significance. While these benchmarks are a sign of a successful clinical trial, individual responses to the dietary treatment are often ignored.

[M]icrobiome-based biomarkers for personalized prognostic, diagnostic, and treatment may vary by geographic locations, lifestyle, and many other factors. Therefore, while personalized microbiome profiling may be useful for predicting and mitigating disease, it will take a huge scientific undertaking before it is ready for the clinical setting.

Decades of generalized nutritional recommendations do not seem to be mitigating the metabolic health crisis, although at present there is no alternate to an overall healthy diet and regular physical activity recommendation for long-term health maintenance.

Even taking into account the huge undertaking discussed above, current knowledge about the microbiome suggests that integrating microbiome profiling into patient care will likely allow for a faster, more accurate, and less invasive clinical decision-making processes. In this context, prebiotics will be critical components of personally tailored dietary interventions aimed at altering the microbiome to a more beneficial configuration for disease prevention.

While the benefits of dietary fibers, many of which have prebiotic properties, are well-known, their mechanisms of action mostly remain a mystery.

Looking to the future, it will be critical to consider the collective effects that are statistically significant, as well as individual response variations, for harnessing the many potential health benefits of prebiotics. Encouraging the scientific community to report variations observed in clinical trials, even if such observations may not meaningfully contribute to the main conclusions of the current study, will be important.

Let’s Discuss

I sense Dr. Dey’s frustration as I read her commentary. She’s been studying the microbiome and noticing small differences that are neither exciting nor statistically significant. In her attempts to understand why these differences occur, she finds nothing in the journals. No one is interested in writing about slight differences, or outcomes that do not support a theory. Probably lots of interesting studies are stopped early or not written up because the researchers found conflicting results or variations that did not fit their conclusions.

I think that these inter-individual differences are most interesting. Why does one person respond well to a spoonful of Bob’s Red Mill potato starch while another sees nothing, or feels bad? Why can one man lose 20 pounds in a couple weeks doing the Potato Hack, while his wife loses nothing and feels terrible?

Beware the Snake Oil

This week, two of my good email buddies shared some information with me. One shared a link to Dave Asprey’s Bulletproof podcast with Naveen Jain. It’s a great interview, have a listen, they discuss how processed foods destroy our gut flora and the dangers of over sanitization. But then I heard “They are gearing up to launch an amazing service to test not just gut but also blood microbiome and then recommend how to balance the issues…”

I’d like to share my response with you all:

The science behind just gut bacteria is so new and so difficult, no one is even close to cracking the code.  To add “blood bacteria” into the mix is just a way to sell a service and products…no way these guys are competent enough to make health claims based on gut/blood bacteria reports.  So, be very, very skeptical of all this!  Right now the prebiotic and gut testing world is like the Wild West.  No real oversight, and lots of trickery, false assumptions, and expensive products.

For gut health, the best anyone can do is just tweak the diet and include lots of fiber that they tolerate.  Potato starch, green banana/plantain flour, Hi-Maize, and inulin/FOS are the four to beat in terms of proven gut benefits.  As everyone has a different starting point, it pays to experiment with these and see which helps the most.  If they leave you gassy and bloated after a week, move on to something else, but also take the time to start slowly and work up the dose to a couple spoonfuls a day.

I’d love to be proven wrong, but I find it highly unlikely that anyone has cracked the bacterial identification code on a level that they can not only correct your gut, but also your blood. My good friend and collaborator Barney should be able to confirm the difficulties of testing bacteria as we’ve spent years studying the methods and information systems involved. Which brings me to the second email I got this week:

Not IMO or Nemo. Cost prohibitive, but ever heard of it?

https://www.isothrive.com/

ISOThrive is gastroenterologist-recommended microFood for the good bacteria in your gut. It is a lightly sweet nectar of prebiotic soluble fiber called MIMO(TM) (maltosyl-iso-malto-oligosaccharides).

What are the ingredients in ISOThrive?
Each sachet of ISOThrive Prebiotic Nectar contains 1g of maltosyl-iso-malto-oligosaccharides (MIMO). These are just zero calorie complex carbohydrates. It’s like calling Vitamin C … Ascorbic Acid. The scientific name sounds weird and scary but it’s not actually weird and scary. ISOThrive is the same ingredient found in naturally fermented foods like kimchi and sauerkraut as well as traditionally fermented sourdough bread.

After several emails discussing and looking for any scientific support, we found this product is used as a sweetener in industrial food processes like many prebiotics (FOS, inulin, etc.). The manufacturers even wrote a paper extolling MIMO’s virtues.

For $59.99 you get a 30-day supply of MIMO sold as IsoThrive. The recommended dose of MIMO is 1 gram per day. The 30-day supply is less than 3TBS!  We’re talking $20 a spoonful. We are to believe that this company has found an artificial sweetener that can shape your gut flora with just 1/3 of a teaspoon a day. Again, I’d love to be proven wrong…but this does not pass my sniff test.

When shaping gut bacteria, it’s a “numbers game.” Realistic doses of prebiotic fibers are more like what Gut Garden’s Resistant Starch blend recommends, a “serving” is about 2TBS (17.96g) or “1 scoop.” Gut Garden recommends starting slow, 1/4 a scoop, and working up to 3 scoops, or as tolerated.

I think as more resistant starch and other prebiotics hit the store shelves, unscrupulous sellers will promise the moon, but recommend doses so low that the fiber will not work as promised. But people will buy these products because of slick marketing.

From Dr. Dey’s commentary, one line stands out:

…at present there is no alternate to an overall healthy diet and regular physical activity recommendation for long-term health maintenance.

Take Home Message

Won’t it be great when science catches up to what we’ve been observing?  I’m thankful that there are professional researchers like Dr. Moul Dey who are not afraid to tell it like it is, acknowledging the shortfalls in the promising field of microbiome modulation. Until it’s settled, eat right, stay fit, and supplement wisely. No amount of supplements will correct a bad diet and a stressful, sedentary lifestyle. Experiment and listen to your gut–it knows what it needs. Watch this space.

Tim Steele

Reference:

Dey, M. (2017). Toward a Personalized Approach in Prebiotics Research. Nutrients, 9(2), 92.

24 Comments on “Toward a Personalized Approach in Prebiotics Research”

  1. Charles A. Richardson February 17, 2017 at 8:05 am #

    Having been in the alternative nutrition biz/world for almost 50 years, my beliefs were shaped early on by “Biochemical Individuality,” by Roger Williams (discoverer of Pantothenic Acid). He makes the case that our individual needs for certain nutrients can vary from 10x to 100x.

    And in my experience in the supplement world, any supplement can be miraculous for some, neutral for others, and harmful to some. It’s almost impossible to predict, so the most important skill to cultivate is being able to evaluate the benefits or harm of any dietary regime yourself. That’s not always easy, given confirmation bias, expectations, the placebo effect, etc. But it’s possible, and critical to taking care of one’s health. That’s not to say we should ignore research, a very important aspect. But in the final analysis, you have to decide what works for you.

    Like

  2. Gemma February 17, 2017 at 10:21 am #

    I’m going to offer testing for your lymphatic fluid microbiome so that the portfolio is complete (that is, almost complete, we are considering testing other bodily fluids in future as well).

    Expect amazing, personalized service and very competitive pricing.

    Like

    • Tim Steele February 17, 2017 at 10:47 am #

      Woo-hoo! Just name your price! Perhaps you can go into business with uBiome as IsoThrive has done: Only $245 per kit! http://amzn.to/2kS2ik3

      “The ISOThrive Gut Health Challenge gives you the first-ever opportunity to feed your beneficial gut bacteria with necessary prebiotic soluble fiber and then scientifically measure and verify how this healthful daily practice affects and changes the organisms living in your gut. “

      Like

  3. Richard Nikoley February 18, 2017 at 9:38 am #

    Excellent, Tim.

    BTW, on the subject of snake oil, I hear there’s now “Bulletproof” WATER with a little snake oil in it.

    Like

  4. Jo tB February 18, 2017 at 9:54 am #

    Why do scientists always want a “one size fits all” answer to their questions? It may make life easier for them, but it doesn’t fit reality. There is a saying: so many people, so many opinions there are. As far as our gut biome is concerned, so many billions of people, so many different biomes there are. Once they start to realise that and put it into practice, the easier it will be for us: a lot less confusion.

    I think that adding personalised different individual responses create a lot of confounding statistics, which are difficult to deal with to get a coherent answer. Is that a bad thing? I don’t think so. The more those statistics get published the more sub groups that will materialise which will be of great help to the patients. At the moment answer A applies to every body. I don’t happen to fit to answer A, so am left in the dark of how to procede.

    Like

    • Tim Steele February 19, 2017 at 7:23 am #

      Big Pharma is only interested in making new drugs, don’t ever forget that! The vast majority of research is done to develop a new drug. All a new drug needs to show is safety and efficacy, it does not need to help everyone that takes it, just some. Then it’s up to doctors to prescribe it, and if it helps any of their patients, and kills only a few, it will be a money-maker.

      There are virtually zero studies being done to help people find ways to cure diseases without pills.

      Like

  5. John Selling February 26, 2017 at 10:31 pm #

    As a practicing gastroenterologist who is also on the clinical faculty at Stanford Medical School, I felt compelled to chime in WRT to your comment on ISOThrive. The ISOThrive product (MIMO) fills a dietary gap that has emerged with the changes in the western diet. Most of us do not get any of this type of prebiotic ever and certainly not in the minimum amounts needed to see a positive effect. MIMO is crafted by bacteria for bacteria and is not found in plant-based foods. As a species we have evolved to require it for the specific subset of bacteria that need it. I have added ISOThrive to my set of “tools” for treating patients and having very good success at dosages of 1g per day. I can understand the skepticism revolving around the relatively small dose compared to the general guidelines for daily fiber intake. First, ISOThrive only feeds a subset of your gut bacteria and not intended to be the only prebiotic in the daily diet. Second, these MIMO molecules are oligosaccharides not starches. Depending on how a starch is broken down in the upper GI tract, it could very likely require many grams of starch to yield 1 g of effective prebiotic, so the gram per gram comparison can lead to misunderstanding. Also, WRT to the length of time to trial a prebiotic needs to be longer than one week. The literature has been fairly clear on this point in that it takes generally two weeks for a shift in activity of newly fed bacteria. Depending on the health state of the colon, it can take several more weeks for repairs to take place and to see a significant positive health effect I would encourage you and your readers to give the product a try especially for reflux esophagitis, chronic constipation, and irritable bowel syndrome.

    Like

    • Charles A. Richardson February 27, 2017 at 8:30 am #

      I looked at your site, and some of the papers. Are there any referring to MIMO specifically?

      Like

    • Tim Steele February 27, 2017 at 8:56 am #

      I look forward to seeing peer-reviewed journal articles on MIMO. As an advisor to ISOThrive, I should hope you will demand comprehensive comparisons of MIMO to other prebiotics such as inulin, FOS, and RS. Specifically, I would be interested in a study designed to show:

      – Bacterial species enriched by MIMO
      – Fungal/Yeast species that can degrade MIMO
      – Capacity of 1g dose of MIMO to have beneficial effects in distal colon
      – Breath-hydrogen testing on SIBO patients after ingesting MIMO
      – Comparison testing of MIMO (6-O-α-isomaltooligosyl-D-maltose) to inulin, FOS, and RS2,3 and 4.

      As it stands, there are zero PUBMED articles concerning the prebiotic capacity of maltosylisomaltooligosaccharides. It’s my opinion that ISOThrive is a biotech company who has simply created a unique method of producing a digestion-resistant oligiosaccharide, and is attempting to create a buzz.

      One claim intrigues me, “It is the only naturally fermented prebiotic that provides the same digestion resistant carbohydrates found in traditionally preserved (fermented) foods such as sauerkraut, kimchi, pickles and slowly fermented sourdough bread. ”

      Are there any references to this anywhere? How much MIMO in an average serving of sauerkraut, etc.?

      Like

    • Gemma February 28, 2017 at 1:44 am #

      “I would encourage you and your readers to give the product a try especially for reflux esophagitis, chronic constipation, and irritable bowel syndrome.”

      “We are very committed to clarity and scientific discovery”

      And what about being committed to actually curing your patients?

      Complex diseases as mentioned above need a COMPLEX approach, that is delivering the right fuel (microbiota accessible carbohydrates, in Sonneburg’s term, preferably from real food) PLUS the right micronutrient co-factors PLUS the microbial genes able to process the delivery, such as in the form of a FECAL TRANSPLANT, for example.

      Ooops. Did I say “cure”?

      The only thing you clearly want to see materialized is an income stream from your “product”.

      That’s why you have visited this site because you know it is full of fibre and microbiome fans, hoping they would jump on your trick.

      Bad luck. I can see right through you. A scientific fraud detected.

      Like

      • Tim Steele February 28, 2017 at 7:25 am #

        You took the words right out of my mouth! Last night, I saw several commercials on TV for prebiotics. They were using all the buzz-words, “microflora,” “beneficial bacteria,” “gut health,” etc. This is a new development! Previously, these same products have been sold as “fiber” for “increasing regularity” and other boring promises.

        I feel the industry is about to explode, and lots of people are wanting in on the ground floor. Consumers will demand jazzy packaging and products that do not cause them to fart. But as you noted, the issue is way more complex. Unfortunately, the winners in this game will be those with the biggest marketing budgets. None of them will want people to know that the answer could be as simple as a green banana or a week of eating potatoes.

        Like

  6. Jack Oswald February 27, 2017 at 12:26 pm #

    I wanted to point out that the ISOThrive paper you referenced is not about extolling the benefits of MIMO. Rather, that paper exposes that commercially available IMO (a very different set of molecules from MIMO) will generally behave like a digestible carbohydrate and result in 80%-100% of it entering the bloodstream, unless “firehose” sized doses are used. You are correct that these IMO products are marketed as a sugar substitute, however, the paper refutes those claims based on their actual digestibility. The ISOThrive product is only marketed as a daily dietary supplement and is not being used as an ingredient. It is not a sugar substitute. We are very committed to clarity and scientific discovery and are working with many of the lead researchers in the field. As you note, ISOThrive may not provide substantial benefits to everyone who takes it. So far, having been on the market for more than a year and several thousand customers, we do know that ISOThrive has been highly effective for the majority of people who try it and realize the value proposition. The best way for you to learn about it is to try it and have others you know try it and see what happens. http://isot.us/jopost

    Like

    • Charles A. Richardson February 27, 2017 at 12:41 pm #

      Here’s some more information about your MIMO and where it came from: http://www.nutraingredients-usa.com/Manufacturers/Brand-aims-to-supply-missing-prebiotic-derived-from-fermented-foods

      Like

    • Tim Steele February 27, 2017 at 12:43 pm #

      Jack – Thanks for the comment and clarification. I’ve been reading the full-text of the paper today. It would have been helpful if the N=2 post-prandial experiment would have also included MIMO alongside glucose and IMO. I agree that IMO is a poor prebiotic, from what I’ve read. But I have seen nothing on MIMO. I could not recommend it to anyone without first seeing some peer-reviewed evidence of it’s effectiveness. There are 30 years of studies on prebiotics such as inulin, FOS, GOS, RS, etc. So I will continue to recommend these over a newly developed fermented maltose product with no published research. In no case have I ever seen a prebiotic fiber being described as beneficial at a daily dose of 1 gram. Small doses such as this would seemingly be fermented by bacteria and fungi in the small intestine or cecum, and certainly not produce much in the way of SCFA. Therefore, the action of MIMO must be completely different from any other prebiotic fiber, can you explain?

      Like

    • Charles A. Richardson February 27, 2017 at 12:47 pm #

      This is apparently the original work at LSU to which you refer: https://www.ibridgenetwork.org/#!/profiles/5045055011535/innovations/13/

      “Isomaltooligosaccharides (IMOs) produced by Leuconostoc mesenteroides ATCC 13146 fermentation with a sucrose:maltose ratio of 2:1 have been discovered to be effective prebiotics in mixed cultures of microbial populations, including cultures from chicken ceca. Surprisingly, in mixed microbial cultures, this IMO composition proved as effective as fructooligosaccharides (FOS). Thus, these IMOs can be used as effective prebiotics for both birds and mammals. Moreover, the IMOs were discovered to be effective non-competitive inhibitors of a-glucosidase. These IMOs also will be useful, as an a-glucosidase inhibitor, in a therapeutic application for several diseases, including obesity, diabetes mellitus, pre-diabetes, gastritis, gastric ulcer, duodenal ulcer, caries, cancer, viral disease such as hepatitis B and C, HIV and AIDS. A diet with 5-20% IMOs was also shown to reduce the abdominal fat tissue in mammals.”

      Like

      • Gemma February 27, 2017 at 12:55 pm #

        “Moreover, the IMOs were discovered to be effective non-competitive inhibitors of a-glucosidase.”

        Aha, now it starts making a bit sense. Acarbose is old news…?

        Besides, our good docs experimenting with MIMO are on this site for a reason. They surely know that potato hack (= eating a few days of extra potatoes) helps to adapt the colon microbiota to maltose oligomers.

        Like

      • Tim Steele February 27, 2017 at 1:23 pm #

        Good find, Charles. “As effective as FOS.” But if our diet contains 5-20% IMO, we get some fat reduction. How many 1g sachets would that be? If MIMO is actually an a-glucosidase inhibitor, perhaps it’s being marketed wrong.

        I believe that the creators of MIMO overlooked some important biology when deciding on dosing. I’ve noticed an industry-wide tendency to use very low doses of prebiotics so that the majority of users do not get adverse reactions. Prebiotics are only effective at doses around 20g. Otherwise there is simply not enough fermentable substrate for SCFA conversion.

        Like

        • Charles A. Richardson February 27, 2017 at 1:38 pm #

          I purchased some, and will try it. I agree the dosage is probably too low to change anything for those of us taking tablespoons of RPS and green bananas! But it’s possible for some who are extremely sensitive, it might help to begin rebuilding. I know someone like that, so I’m going to let her try it, and see if there’s noticeable benefit.

          Like

          • Tim Steele February 27, 2017 at 2:28 pm #

            Keep us posted! I’d like a bit more details before I’d recommend such a product. The FAQs at the site are very vague:

            “…feed the beneficial bacteria in your digestive system.” Which bacteria? Have studies been conducted? Can we see them?

            The “Nerd Page” which is supposed to be hundreds of studies on MIMO is just a laundry list of prebiotic research, none of which describe the efficacy of MIMO.

            Basically, what I see is that there is a compound isolated in fermented foods and mimicked by fermenting glucose/maltose with Leuconostoc mesenteroides and the resultant sweet syrup is trademarked at MIMO. Is MIMO effective without the accompanying acetic and lactic acid, resistant starch, or cellulose found in fermented breads and cabbage? This smacks of resveratrol to me. A promising compound, yet ineffective without the rest of the grape.

            I’m really, really curious how much “MIMO” is found in a bowl of kimchi or a slice of organic, heirloom, sourdough bread. As there is no literature describing this, we are at the hands of ISOThrive to tell us.

            Like

            • Charles A. Richardson February 27, 2017 at 2:42 pm #

              As I suggested above, as a maintenance supplement, maybe not. But as a beginning therapeutic dose for someone with a very damaged microbiome, maybe it’s a good starting point. We’ll see in an N=1 if it makes any difference.

              Like

  7. Wilbur March 1, 2017 at 5:47 am #

    I don’t know where to put this, but here’s a new personalized probiotic approach to help eczema, maybe.

    https://www.theatlantic.com/science/archive/2017/02/a-personalized-probiotic-skin-cream-made-with-a-persons-own-microbes/517473/

    Like

  8. gina March 3, 2017 at 5:01 pm #

    I don’t know where to put this. But I am wondering if anyone has heard of potato cheese before? This is kind of a weird ferment:

    https://kitchencounterculture121.wordpress.com/2017/03/02/potato-cheese-a-19th-century-english-ferment/

    Like

    • Tim Steele March 3, 2017 at 5:08 pm #

      Incredible! Never heard of such a thing. I’m not brave enough to try! Any takers?

      Like

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