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"Obligatory" consumption of probiotics as a strategy to enhance general health

Image credit: https://www.pexels.com/photo/pineapple-next-to-bowl-2064692/

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Juranium Nov 04, 2020
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Necessity

Is the problem still unsolved?

Conciseness

Is it concisely described?

Iodisation of table salt started early in the 1920's to reduce the iodine deficiency affecting the mental and physical development in humans.

Due to all the beneficial effects of balanced gut microbiota, should we implement the consumption and use of small concentrations of probiotics through "probioticsation" of e.g. dairy products, flour, sunscreens, etc.?
Would it bring an overall increase in human healthspan or life quality?


Human microbiota consists of bacteria, fungi, archaea and viruses, which seem to play a very important role in keeping us healthy and happy. How?
  • Gut microbiota changes affect the chemotherapy outcome
  • Improving gut microbiota balance could help you sleep better
  • Gut microbiota from thin people could make fat people lose weight
  • Fecal transplantation to cure diseases (brainstorming session about it)
Balanced microbiota is also beneficial to the other parts of the body:
  • Colonization of mice with a specific Staphylococcus reduced the incidence of UV-induced skin neoplasia
  • Oral microbiota highly related to oral and gastroenteric cancers
  • Specific vaginal microbiota affect HIV medication efficiency
There are plenty of products on the market which contain or are enriched with probiotics.


Do they actually work?
Can we find a generally useful mix of microbiota that could be beneficial to 99% of people and implement it in everyday food consumption, like it was done with iodine?
What are the downsides of proposed "probioticsation"?

[1]https://www.nature.com/articles/nrgastro.2017.20

[2]https://www.theguardian.com/lifeandstyle/2018/mar/19/is-your-gut-keeping-you-awake-at-night

[3]https://www.theguardian.com/society/2013/sep/05/bacteria-slim-treat-obesity-study

[4]https://www.theguardian.com/science/2013/mar/31/bacteria-faecal-transplant-gut-mary-roach-gulp

[5]https://advances.sciencemag.org/content/4/2/eaao4502

[6]https://openmicrobiologyjournal.com/VOLUME/14/PAGE/1/

[7]https://www.sciencedaily.com/releases/2017/06/170601151924.htm

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Creative contributions

Extensive quality control and risk-benefit ratio are major restrictions in generalization of probiotics

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Kritika Bansal Nov 11, 2020
Every probiotic formula is effective depending on its dose, the specificity of the product, the way it has been manufactured, the group of strains used, the duration for which it needs to be taken etc . Considering so many parameters are required to establish the efficacy of probiotics, and the fact that combination of strain that can be used are manifold, a large scale clinical research will be needed to be laid down to develop a product that can be "generalized".

From the population point of view, any probiotic can entail the risks of infection and toxicity which further depends on the immunological status of the recepient. Even the method of administration of probiotic may elicit an unwanted respose in one recepient but not in other . So not only geography, ethinicity and diet patterns need to be categorized for generalization, even the immunological status needs to be considered that just increases the scope of a clinical research manifold.

Even though probiotics are popularly known to be safe, any adverse effects so far reported can become a major milestone in generalizing probiotics.

Extensive data collection from patients, some sort of biomarkers reflecting on immunological status of an individual might prove to be major step in strategizing a generalized probiotic.

[1]de Simone C. The Unregulated Probiotic Market. Clin Gastroenterol Hepatol. 2019 Apr;17(5):809-817. doi: 10.1016/j.cgh.2018.01.018. Epub 2018 Mar 14. PMID: 29378309.

[2]Sanders ME, Akkermans LM, Haller D, Hammerman C, Heimbach J, Hörmannsperger G, Huys G, Levy DD, Lutgendorff F, Mack D, Phothirath P, Solano-Aguilar G, Vaughan E. Safety assessment of probiotics for human use. Gut Microbes. 2010 May-Jun;1(3):164-85. doi: 10.4161/gmic.1.3.12127. Epub 2010 Mar 4. PMID: 21327023; PMCID: PMC3023597.

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Juraniuma year ago
I completely agree.
Also, no study, proof, or law will erase the general fear that the term bacteria causes.

What I thought is that maybe an invisible dose - an almost insignificant amount of known beneficial bacteria could be a good entry point to "start the wave" and also have a hormetic effect. But the amount must be so small that even if someone eats/drinks 10x the recommended dose, nothing bad happens.
So finding a dose below all reported doses that caused adverse effects and implementing it in the strategical market solution.
What do you think about that?

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Will the "obligation" work?

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 05, 2020
I agree that probiotics are really helpful to lead a healthy life. I am not sure whether the "obligation" on their use will work when individual free (-dom/ -will) are gaining more and more importance. The Covid-19 vaccine will help us judge (if it is made obligatory) whether people "obey".
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Juraniuma year ago
I ran on an interesting paper that could serve as an argument about why this kind of "health obligations" could work.

Scientists studied the indirect genetic effects of 80,889 human couples of European ancestry (https://www.nature.com/articles/s41562-020-00991-9#code-availability). They wanted to see if an individual's behavior can be influenced by the individuals around us. When they filtered results that could have been the result of "an assortative mating" (e.g tall people choosing tall partners), they found that several behavioral traits strongly influenced the other person's phenotype. The associations included poultry and beef intake, time spent watching TV, susceptibility to mood swings, and smoking habits.

What it means is that there is a possibility that we can indirectly, by our behavior or "phenotype", influence the other person's genome. Thus, by the adoption of healthy habits or healthy dietary routines, there is a possibility of benefit not only for us but also for the people close to us.
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Povilas S
Povilas Sa year ago
With covid it's a bit different because you also endanger other people (although I'm not sure if this is the case when it comes to vaccination), but with probiotics, it would mostly be about your own health so it's even more intense regarding the freedom. In the US and some other countries, fluoride is put into tap water, so everyone consumes it whether they want it or not, this is a strategy for improving public dental health, but in my opinion, it's a bad strategy. Some people are against using fluoride as a supplement and indeed there are negative effects linked with its consumption, of course with larger doses, but still. Those kinds of actions also become very good soil for conspiracy theories to grow. So this would be the same with probiotics. Why force people? Better educate them well and let them choose. As long as you're not harming others it should be your choice.
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Juraniuma year ago
Good point! Although in very specific places, you can still buy non-iodized salt in some shops. That could be a nice strategy - to leave the decision to people. Give them scientific data about probiotic benefits and let them choose in the market.
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What about people allergic to certain foods?

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 05, 2020
Even though you mentioned dairy products as an example, I am wondering how many foods can accommodate probiotics. Most of them will be allergic to a certain population. How do you then regulate the doses? If a 20-year old individual should be consuming x amount of probiotics, and a regular glass of the "probiotic" milk provides that x amount, they need to consume it. What if the individual is intolerant and has to rely on some other food for their daily intake?

Generalizing seems to go the opposite way when the worldly tendency today is to develop personalized products and even medicines and medical therapy.
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Juraniuma year ago
I would first look at how current probiotic products dealt with this issue. The products would consist of small doses of probiotics that are beneficial to the whole population, or would, as cat/dog food, be categorized according to the age.

If an individual is intolerant, then it could use chocolate bars, flour, or something not-diary, but still enriched with probiotics.

Although I see many beneficial effects of this idea, I must agree your last paragraph is of my biggest concern. Analyzing the individual´s stool and then tailoring the personalized probiotic could be a better way.
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Probiotic foods with specific bacteria

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Shubhankar Kulkarni
Shubhankar Kulkarni Nov 18, 2020
The ultimate aim is to personalize the probiotic. Ideally, there will be a vending machine/ a dispenser that creates a probiotic for you after you put in your credentials. Your physician will already have prescribed you a type and dose of probiotics that will be in the system. The machine will add the prescribed ingredients to your choice of food (based on your allergies) and serve it.

Till we reach that point, we can have foods with specific bacteria. For example, when manufacturing yogurt, there can be regular as well as probiotic yogurts. Moreover, in the probiotic yogurts, there will be yogurts that contain only Ruminococcus or only Roseburia. To simplify the manufacturing process and decrease the SKUs, there can be yogurts that contain multiple bacterial species that are usually found to go together. Physicians can then prescribe the bacterial species that you need to take and then you buy those. There can be few other foods that can carry probiotics for people intolerant to yogurt.
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Juraniuma year ago
The idea could work, but if it will be vending machines or dispensers doing that, it would be even less probable that people will trust these products. Food in vending machines sometimes stays for few weeks until someone buys it. Plus, the system should be sterile as a lab. Therefore, I would rather propose the "probiotic machines" in certain pharmacies, where the process can be monitored and where people would trust the product more.
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Shubhankar Kulkarni
Shubhankar Kulkarnia year ago
Juran K. Agreed! Such machines in pharmaceutical stores would be more trusted. However, I think that limits sales. More people visit grocery stores than the pharmacy. And since the idea is to make probiotic foods, would it be better to have the products in the grocery store? I would like to know your opinion on the second paragraph in my suggestion. It is a more feasible idea than the vending-machine one. Also, the idea eliminates all the problems with generalizing the probiotic constituents in the foods. People can then buy the probiotics (microbes) that they need at their age, geographical location, race, sex, etc. They can buy multiple products based on the prescriptions given by their physicians.
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Juraniuma year ago
Shubhankar Kulkarni I agree with the limitation of the sales you mentioned. Grocery stores would be the best.

Concerning the second paragraph, that is exactly what we need. From the start, there would be only a few options available, but with more research being done, new, more specific products could emerge., at the end resulting in all varieties of probiotic yogurts available (based on your specific needs). It could be done with other everyday products such as coffee milk, coconut and almond milk, smoothies, protein bars, etc. But, in my opinion, it should only be available on prescription, at least at the beginning.

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Categorise diet patterns, geographical and ethnic groups before administering

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Subash Chapagain
Subash Chapagain Nov 05, 2020
One of the main concerns when administering such 'generalized' probiotics in an obligatory manner would be regarding the interplay between the newly introduced strains in the probiotic food and the already existing microbiota in the individual's body. It is a very well established premise that our geographical location, ethnicity and dietary patterns are the chief determinants of our gut microbiome. People living in western countries usually take diet low in fiber and consume a high amount of fat and refined carbohydrates compared to the eastern countries where rice, noodles, soup, vegetables and fish contain a major portion .

This kind of variability in the diet influences the microbiome populations and their diversity among the individuals. It has been demonstrated that the Bacteroides enterotype is increased in the guts of people living in Western countries eating a western diet with high fat and protein content, while Prevotella enterotype is common in non-Western countries where the population consumes lots of fiber .
At the genus levels, Japanese showed high abundances of Bifidobacterium and Clostridium, Chinese of Bacteroides and Korean of Prevotella and Faecalibacterium in their gut microbiome. There is a dominance of Prevotella in Malawi, Venezuela, and Peru; Bacteroides in USA, China, Denmark, Spain, and France; Eubacterium in Russia; Clostridium in Sweden and Blautia in Austria. Bacteroides genus dominated in American and Jamaican populations while Prevotella genus dominated in Indian population. Ruminococcus, Roseburia, Veillonellaceae dominated in the gut microbiome of healthy individuals from the Netherlands. Such country-wise and geographical variations can make it difficult to prepare an all-applicable mix of probiotics like you proposed in the session.
Hence, a better approach would be to categorise people based on the variables like ethnicity, dietary patterns and geography and then only preparing a probiotic tailored to each specific groups. This might mean that some species of bacteria should be included in a higher ratio in some mix and some other strains be absent. With this model, we can tweak the levels according to the clinical features of the category and administer accordingly.

[1] A.B. MothersheadDining customs around the world Garrett Park Press, Maryland (1982), p. 150

[2] A.B. MothersheadDining customs around the world Garrett Park Press, Maryland (1982), p. 150

[3]Gupta VK, Paul S, Dutta C. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity. Front Microbiol. 2017;8:1162. Published 2017 Jun 23. doi:10.3389/fmicb.2017.01162

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Juraniuma year ago
Subash ChapagainThank you for your contribution!

I completely agree. The categorization you mentioned is of incredible importance and would be the first step in this process.

I didn´t know about countries' variabilities in the microbiome being this big. It would be nice to see if this correlates with climate, diet, ethnicity, and cluster people in specific groups. Good point!

I was just thinking, what if, for e.g., some people live longer because they have better gut microbiota? Wouldn´t it be good to change the microbiota of other people to something more similar to the long-living ones?
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Shubhankar Kulkarni
Shubhankar Kulkarnia year ago
Juran K. You are right. There do exist significant differences in the gut microbiota of the long-lived people when compared to controls. There also exists a difference across geographical regions and countries. One study observed a common link across long-lived people from different regions. Their comparative analysis showed that there is higher biodiversity within the Ruminococcaceae family in centenarians, compared to younger adults, irrespective of their nationality. Bacterial signatures were common among extremely old people of different nationalities. They identified Akkermansia, Alistipes, and Ruminococcoaceae D16 as signature taxa of long-lived people. Their results also suggested a change in the gut ecology during extreme aging from their younger counterparts. That change may be one of the keys to a long life.

Reference: I strongly encourage you to look at figures 2 and 3 from the study report. https://www.sciencedirect.com/science/article/abs/pii/S0047637418302057
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Juraniuma year ago
Shubhankar Kulkarni This could be a way to extract a new "healthy aging" checkpoint - biochemical changes and processes related to the specific microbiota activity in the gut of centenarians.
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Probiotics vs depression?

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Juranium Dec 16, 2020
Scientists correlated major depressive disorder (MDD) to the specific composition of bacteria, viruses, and their metabolic products .


Chinese researchers collected fecal samples of 236 people, of which almost half had diagnosed, but not treated, MDD. By total genomic DNA sequencing of the samples, they managed to find a correlation between MDD and gut microbiome composition.

The results showed a higher abundance of 18 bacterial species (Bacteroides), while 29 were less common in MDD samples (Blautia, Eubacterium). Team also found three bacteriophages with different levels in healthy and MDD samples. The molecules that are produced by the microorganisms were analyzed using gas chromatography-mass spectrometry (GC-MS). In total, 16 metabolites were significantly more and 29 significantly less represented in MDD samples, most of them related to amino acid metabolism (gamma-aminobutyric acid (GABA) metabolism, phenylalanine metabolism, and tryptophan metabolism).

Then the team constructed an MDD biomarker panel consisted of 2 bacteria, 2 bacteriophages, and 2 metabolites and tested it on a sample of 75 subjects. They were successful in determining the MDD with an accuracy of 90 %.

How could the gut microbiome be related to the MDD?
Scientists suggest that the neurotransmitter called GABA could be the key. GABA and its metabolites were less abundant in MDD samples. In addition, genes related to GABA were altered in MDD, compared to the healthy samples. Interestingly, studies showed that when the gut microbiome of the MDD person is transplanted into a healthy rat, it starts to show the signs of depression.

It could definitely be the other way around - that depressed people change their dietary habits and that way influence the gut microbiome, but it is more likely that is bi-directional relation.

Why does it matter?
If added in safe concentration, certain microbial species could help not only prevent obesity, diabetes, or similar disorders related to the metabolism but also to lower the prevalence of mental diseases such as depression.

[1]Yang J, Zheng P, Li Y, Wu J, Tan X, Zhou J, Sun Z, Chen X, Zhang G, Zhang H, Huang Y, Chai T, Duan J, Liang W, Yin B, Lai J, Huang T, Du Y, Zhang P, Jiang J, Xi C, Wu L, Lu J, Mou T, Xu Y, Perry SW, Wong ML, Licinio J, Hu S, Wang G, Xie P. Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders. Sci Adv. 2020 Dec 2;6(49):eaba8555. doi: 10.1126/sciadv.aba8555. PMID: 33268363; PMCID: PMC7710361.

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Two approaches to tackle the long-term stability of the probiotic products

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Juranium Dec 17, 2020
The most popular probiotic bacteria are Lactobacillus and Bifidobacterium. They are naturally occurring species of the human gut and extensively investigated. However, they are not stable at room temperature and do not survive long-term storage. To tackle this problem, scientists channelize their research into two different directions:
  1. Development of encapsulation methods
  2. Exploring new microbial species

Development of encapsulation methods

Scientists try to develop new coatings or matrices which will allow bacteria to safely reach the gut where they should act. New synthetic or natural materials, such as alginate, carrageenan, gelatin, chitosan, whey proteins, cellulose acetate phthalate, locust bean gum, starches, and others, protect the bacteria from being digested in the stomach or the bile, thus protecting the host from the potential bacterial colonization of unwanted body compartments. In addition, new materials preserve bacterial viability on the shelf, allowing long-term storage .

Pluses
  • Incorporation of microorganisms in food (dairy products, ice cream, ...)
  • Improved survival in frozen dairy products
  • Improved survival in the gut
Minuses
  • Increased costs of probiotic production (development of the material, encapsulation method, and testing in various conditions)

Exploring new microbial species

On the other hand, researchers focus on the survival properties of other bacterial species. One such species is Lactobacillus sporogenes (aka L. coagulans). It inhabits the gut and produces lactic acid. It was shown that the abundance of L. sporogenes is drastically lower in the pathogenic gut conditions, allergies, and eczemas. Compared to Lactobacillus and Bifidobacterium, L. sporogenes produce spores, which allows them to survive in the harsher conditions (heat, dryness), including long-term storage .

Pluses
  • Incorporation of microorganisms in many food types (dairy products, ice cream, coffee, tea, oils, ...)
  • Improved survival in frozen, processed, and long-storaged products
  • Improved survival and easier delivery to the gut
Minuses
  • Well, ...

As @Shubhankar mentioned in the contribution above, these findings could allow probiotic products to be stable in the long-term and thus distributed throughout vending machines in grocery stores. It also potentiates further investigation on probiotic safety, which could finally lead to the general usage of probiotics on a national level as a health measure.

[1]https://www.researchgate.net/publication/223308503_Recent_advances_in_microencapsulation_of_probiotics_for_industrial_applications_and_targeted_delivery

[2]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763591/

[3]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834910/

[4]https://pubmed.ncbi.nlm.nih.gov/28763015/

[5]https://www.sciencedirect.com/science/article/pii/S0963996918309505

[6]https://ifst.onlinelibrary.wiley.com/doi/full/10.1111/ijfs.13044

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L. sporogenes led to probiotic coffee, tea, chocolate, soup, pasta, sugar and much more

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Juranium Dec 18, 2020
Until recently, you could buy only probiotic pills or food such as joghurt, milk or other diary product. Nowadays, by exploiting the extraordinary properties of Lactobacillus sporogenes (coagulans) MTCC 5856, we see more and more different foods enriched with probiotics.

These bacteria are usually found in the human gut and are known to form spores, unlike the other bacteria used in probiotic products (Lactobacillus and Bifidobacterium). Spores can survive in harsh conditions such as increased heat, dryness, and others. When back in a suitable environment, these spores activate and live bacteria form . Although the bacteria was found two decades ago, the benefits of its general use in therapies and everyday consumption have just recently regained interest, resulting in numerous products such as Sporlac (Sankyo Co. Ltd), LactoSpore (Sabinsa Ltd), Bacillus Coagulans (Thorne Research Ltd) and others.

Functional properties
L. sporogenes MTCC 5856 in coffee and tea after brewing showed viability of 94.4% and 99%, respectively, even after additional short-term storage. Also, the species showed more than 90% viability after the brewing and long gastric mimicking treatments. Importantly, no significant differences were observed in the sensory profile of brewed tea or coffee with L. coagulans MTCC 5856. Coffee and tea powder enriched with L. sporogenes MTCC 5856 also showed long-term stability at room temperature of incredible 24 months .

Clinical research
Research in Japan on 567 patients reported statistically significant improvements of symptoms caused by gastrointestinal abnormalities (diarrhea, constipation, mal-digestion) after the L.sporogenes consumption. Similar research reported good response of neonatal diarrhea patients to L. sporogenes therapy .

Safety of consumption
Research from 2016 evaluated safety of LactoSpore product through double-blind , placebo-controlled experiment on 40 participants and verified that no adverse events or any unwanted changes in laboratory parameters, bowel movements or the Bristol stool scores were osberved after 30 days of 2 × 10^9 cfu/day consumption . Similar conclusion was drawn from the pilot clinical study, also in 2016 . Furthermore, reported by the Finnish study of lactobacilli bacteremia, "the increased usage of probiotic products of lactobacilli did not cause any increase in incidence or frequency of bacteremia in Finland" .

Products
Nowadays, besides dairy products, you can find all varieties of probiotic food products such as:
Probiotic fruit juices
Probiotic cane sugar
Probiotic reef salt
Probiotic chocolate
Probiotic Ginger Beet (Farmhouse Culture)
Probiotic Kimchi (Farmhouse Culture)
Probiotic Naturally Caffeine Free Herbal Tea (Traditional Medicinals)
Probiotic Soft Chews (sweets , bonbons) (Bariatric Fusion)
Probiotic Coffee
Probiotic soup
Probiotic Pasta
* type of food that I thought about at the beginning of the session

What do you think?
Could probiotic pasta, sugar or salt become everyday consumables like iodized salt?

[1]https://www.sciencedirect.com/science/article/pii/S0963996918309505

[2]http://beta.rodpub.com/public/uploads/263888lactospore.pdf

[3]https://www.researchgate.net/publication/298661972_A_Double-Blind_Placebo-Controlled_Parallel_Study_Evaluating_the_Safety_of_Bacillus_coagulans_MTCC_5856_in_Healthy_Individuals

[4]https://pubmed.ncbi.nlm.nih.gov/26922379/

[5]https://pubmed.ncbi.nlm.nih.gov/12410474/

[6]https://www.amazon.com/Sugar-2-0-Probiotic-16-oz/dp/B01DK2V4YA

[7]https://aquaforest.eu/en/product/probiotic-reef-salt/

[8]https://www.amazon.com/Bouchard-Belgian-Gluten-Free-Chocolate-Probiotics/dp/B07H5TCX9S

[9]https://www.sakara.com/products/probiotic-chocolate

[10]https://www.amazon.com/BeLive-Probiotic-Digestive-Vitamins-Supplement/dp/B06ZZPS4Q9

[11]https://www.trendhunter.com/trends/coffee-and-probiotics

[12]https://www.lizmoody.com/sweet-sour-probiotic-soup/

[13]https://www.nutraingredients.com/Article/2015/11/30/Probiotic-pasta-developed-by-Italian-researchers

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