Is collagen hydrolysate/gelatin a prebiotic for your gut microbes and what are the other prebiotic foods to best feed the gut microbes?

‘What are the other prebiotic foods to best feed the gut microbes?’

There is more hype than substance to claims that something or the other is a prebiotic that best sustains healthy gut microbiota since the latter itself lacks universal definition, is far from generalizable, and is largely the product of genetics, diet, lifestyle, age and gender, to name just a few of the most important factors. In fact, as recently as 2011 the European Food Safety Authority - Wikipedia (EFSA) stated (1, emphasis mine),

'based on current scientific knowledge, it is not possible to define the exact numbers of the different microbial groups which constitute a normal microbiota. The evidence available to the Panel does not establish that increasing the number of any groups of microorganisms, including lactobacilli and/or bifidobacteria, is in itself a beneficial physiological effect. For function claims related to changes in gastro-intestinal microbiota these changes should be accompanied by a beneficial physiological or clinical outcome.'

No wonder there is even less clarity with regard to Prebiotic (nutrition) - Wikipedia, compounds indigestible by human gut epithelial cells but digestible by specific bacteria. Especially pertinent since the major marketing claim for most commercial products touting prebiotic benefits is their capacity to support 'healthy intestinal microflora'.

How Prebiotics Might Help Sustain Beneficial Gut Microbes: Some Data And Unresolved Issues

Gut microbes digest prebiotics, increasing the rate of their metabolic products such as lactic acid and other fermentation products. These in turn reduce local gut lumen pH and encourage the growth of other microbes capable of utilizing such fermentation products and so on. Over time, this process builds a network of mutually interdependent microbial species but its potential to change the entire gut ecosystem starts with the initial human cell-indigestible component(s), i.e., prebiotic. However, causal relationships between prebiotic-driven microbiota changes and health effects still remain speculative and unproven. That definition of prebiotics keeps changing only serves to emphasize their study is nascent.

• For example, Glenn R. Gibson and Marcel B. Roberfroid originally defined prebiotics in 1995 as (2),

'a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health’

• Modified in 2004 (3) to

'A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microbiota that confers benefits upon host wellbeing and health’

• And modified yet again in 2010 (4) to

'selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health'

Such frequent definition changes engender confusion among consumers, prevent uniform, comparable scientific studies from being pursued, and prevent consensus formation between scientists, regulators, food industry and healthcare professionals (5).

The type of effects we should expect from prebiotics also remain unclear:

• Increase in some specific bacteria, say, Faecalibacterium prausnitzii or bifidobacteria or lactic acid bacteria or just increase in bacterial diversity? Is increase in bacterial diversity a generalizable health benefit?
• Increase in a specific output, say, fermentation or Short-chain fatty acid - Wikipedia (SCFA) or many other effects also possible?
• Which is more important, dose or frequency?
• How equivalent are natural prebiotics versus supplements? Are their effects even comparable?
• What about effect on immune function? Is it direct or indirect, by selectively binding and eliminating pathogens, i.e., Colonisation resistance - Wikipedia?
• Don’t responses varying between individuals preclude generalization?
• Different people respond differently to the same prebiotic (6, 7).
• Specifically Inulin - Wikipedia didn't uniformly increase gut bifidobacteria in all those who took them, with levels staying low in some who started out with low numbers (6).
• Response to prebiotics is also different between healthy and ill people (8) and between those lean versus obese (9).

Examples Of Some Substances Commonly Accepted As Prebtioics

Currently identified prebiotics are carbohydrates though this doesn't preclude other compounds such as proteins from being found to have prebiotic properties in future (8). Human breast milk is a classic prebiotic with substantial evidence of health benefits, specifically promotion of bifidobacteria colonization of infant gut (10, 11). Thus far the most robust list of physiological effects is available for Fructan - Wikipedia (12, also see table below from 13). Other broadly accepted prebiotics are Fructooligosaccharide - Wikipedia (FOS) and Galactooligosaccharide - Wikipedia (GOS).

• Inulin-type fructans are abundant in chicory root and Jerusalem artichoke (12, 13).
• Natural FOS are found to varying degree in banana, garlic, honey, onion, wheat (13, 14).
• Natural GOS are abundant in pulses (Legume - Wikipedia) (12).

‘Is collagen hydrolysate/gelatin a prebiotic for your gut microbes?’

No. Thus far no proteins have been labeled prebiotic. Obviously, being indigestible and fermentable are criteria unlikely to be fulfilled by most proteins.

Collagen is the most abundant structural protein in animals, constituting ~30% of total animal protein (15). Primarily derived from the Collagen in connective tissue, bone and skin, Gelatin is a high molecular weight protein that unfolds when melted and cools into a water-trapping helix-coil structure that forms a reversible gel. Consider Jell-O - Wikipedia, the ever-present dessert. Though it looks solid, it's actually >99% liquid.

While it's been part of our diet for centuries, the industrial revolution made gelatin practically ubiquitous, from foodstuffs to photography (think glossy photo paper) to glues to pharmaceuticals. Being amphoteric (Amphoterism - Wikipedia), having a variable Isoelectric point - Wikipedia as well as capacity for Coacervate - Wikipedia (separation of colloid particles from a solution) makes gelatin ideal for Micro-encapsulation - Wikipedia, hence its ubiquity in industrial food and pharmaceutical products (as capsules, sponges, Excipient - Wikipedia for example). Other advantages include (16)

• Easily digestible, high quality protein containing neither carbohydrates nor fats.
• Gluten-free.
• Extremely low allergenic potential.
• Clinical studies have shown special types of gelatin, marketed as collagen hydrolysate, can have a protective effect on joint cartilage (15). Hence its wide prevalence as a food additive for osteoarthritis patients and athletes.

Could Gelatin Be A Prebiotic? No Evidence Yet To Support Such A Possibility.

Though it's ubiquitous in the food industry, no systematic efforts have assessed if gelatin has prebiotic qualities. For example, as recently as 2015-2016, comprehensive reviews on collagen and gelatin list their major potential biological effects as antioxidant, antihypertensive, anticancer, antiphotoaging and cholesterol-lowering (15, 17) with no mention at all of prebiotic capacity.

However, neither is this unsurprising since most confirmed prebiotics tend to be poorly digested carbohydrates. Since carbohydrates yield certain defined effects such as fermentation, lactic acid, etc., efforts to identify new prebiotics focus on capacity to do likewise. It's entirely possible such a 'looking under the lamp post approach' may impair uncovering novel classes of prebiotics, which may not generate fermentation products or SCFA and yet be indigestible or primarily digested by gut microbes and have beneficial gut microbe and health effects.

Reports of gelatin's direct effect on microbes are meager.

• Gelatin strongly supports the growth of many microbes (16). This is why extremely stringent ISO9000-compliant quality control procedures are necessary during its industrial-scale manufacture.
• At least one known Probiotic - Wikipedia, (microbes with proven health benefits), namely, Bacillus clausii - Wikipedia (https://microbewiki.kenyon.edu/i...), can hydrolyze Gelatin. A soil bacterium first described in 1995, its probiotic properties are currently the focus of active research (18).

A few clinical studies have noted oral Gelatin/Collagen hydrolysate can influence appetite, suppressing it in the short-term (19) but not in the long-term (20), influence weight (21), again not in the long-term (22), and improve skin texture (23, 24, 25, 26). None of these studies have even speculated the observed biological effects could be due to effects on gut microbes.

Bottomline, as of 2016 there appear to be no scientific studies that have explicitly, comprehensively and systematically examined if and what effect Gelatin/Collagen hydrolysate have on gut microbiota, let alone explored the possibility they may have prebiotic effects.

Bibliography

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3. Gibson, Glenn R., et al. "Dietary modulation of the human colonic microbiota: updating the concept of prebiotics." Nutrition research reviews 17.02 (2004): 259-275.

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7. Louis, Petra, et al. "Diversity of human colonic butyrate‐producing bacteria revealed by analysis of the butyryl‐CoA: acetate CoA‐transferase gene." Environmental microbiology 12.2 (2010): 304-314. https://www.researchgate.net/pro...

8. Whelan, Kevin. "Mechanisms and effectiveness of prebiotics in modifying the gastrointestinal microbiota for the management of digestive disorders." Proceedings of the Nutrition Society 72.03 (2013): 288-298. https://www.cambridge.org/core/s...

9. Aguirre, Marisol, Carlota Bussolo de Souza, and Koen Venema. "The gut microbiota from lean and obese subjects contribute differently to the fermentation of arabinogalactan and inulin." PloS one 11.7 (2016): e0159236. http://journals.plos.org/plosone...

10. Mueller, Noel T., et al. "The infant microbiome development: mom matters." Trends in molecular medicine 21.2 (2015): 109-117. http://www.ncbi.nlm.nih.gov/pmc/...

11. Chichlowski, Maciej, et al. "Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function." Journal of pediatric gastroenterology and nutrition 55.3 (2012): 321. http://www.ncbi.nlm.nih.gov/pmc/...

12. Louis, Petra, Harry J. Flint, and Catherine Michel. "How to Manipulate the Microbiota: Prebiotics." Microbiota of the Human Body. Springer International Publishing, 2016. 119-142. Microbiota of the Human Body

13. Schaafsma, Gertjan, and Joanne L. Slavin. "Significance of inulin fructans in the human diet." Comprehensive Reviews in Food Science and Food Safety 14.1 (2015): 37-47. https://www.researchgate.net/pro...

14. Belorkar, Seema A., and A. K. Gupta. "Oligosaccharides: a boon from nature’s desk." AMB Express 6.1 (2016): 82. Oligosaccharides: a boon from nature’s desk

15. Liu, Dasong, et al. "Collagen and gelatin." Annual review of food science and technology 6 (2015): 527-557.

16. Schrieber, Reinhard, and Herbert Gareis. Gelatine handbook: theory and industrial practice. John Wiley & Sons, 2007. Gelatine Handbook

17. Koyama, Y. "Effects of Collagen Ingestion and their Biological Significance." J Nutr Food Sci 6.504 (2016): 2. http://www.omicsonline.org/open-...

18. Felis, Giovanna E., Franco Dellaglio, and Sandra Torriani. "Taxonomy of probiotic microorganisms." Prebiotics and probiotics science and technology. Springer New York, 2009. 591-637.

19. Hochstenbach-Waelen, Ananda, et al. "Single-protein casein and gelatin diets affect energy expenditure similarly but substrate balance and appetite differently in adults." The Journal of nutrition 139.12 (2009): 2285-2292. Single-Protein Casein and Gelatin Diets Affect Energy Expenditure Similarly but Substrate Balance and Appetite Differently in Adults

20. Hochstenbach-Waelen, Ananda, et al. "Effects of a supra-sustained gelatin–milk protein diet compared with (supra-) sustained milk protein diets on body-weight loss." British journal of nutrition 105.9 (2011): 1388. https://www.researchgate.net/pro...

21. Rubio, I. G. S., et al. "Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in obese patients: Postprandial effect on circulating gut peptides, glucose and insulin." Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity 13.1 (2008): 48-53.

22. Hochstenbach-Waelen, A., et al. "No long-term weight maintenance effects of gelatin in a supra-sustained protein diet." Physiology & behavior 101.2 (2010): 237-244.

23. Tanaka, Midori, Yoh-ichi Koyama, and Yoshihiro Nomura. "Effects of collagen peptide ingestion on UV-B-induced skin damage." Bioscience, biotechnology, and biochemistry 73.4 (2009): 930-932. http://www.tandfonline.com/doi/p...

24. Proksch, E., et al. "Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study." Skin pharmacology and physiology 27.1 (2013): 47-55. https://www.researchgate.net/pro...

25. Proksch, E., et al. "Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis." Skin pharmacology and physiology 27.3 (2013): 113-119.

26. Schunck, Michael, et al. "Dietary Supplementation with Specific Collagen Peptides Has a Body Mass Index-Dependent Beneficial Effect on Cellulite Morphology." Journal of medicinal food 18.12 (2015): 1340-1348. https://www.ncbi.nlm.nih.gov/pmc...

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