Probiotics and digestive enzymes: how they can improve nutrition

Probiotics and digestive enzymes: how they can improve nutrition

Probiotics and digestive enzymes are two popular dietary supplements While there are differences between the role of digestive enzymes and probiotics, both compounds have been praised for their improvement on digestive health. Learn what probiotics and digestive enzymes are, where to find them, and how they may improve nutrition.

What are Digestive Enzymes

Digestive enzymes are part of the digestive system. These substances are produced and secreted by the body. They are commonly found in the mouth, stomach, pancreas, and intestines [R]. 

How Do Digestive Enzymes Work?

During the digestive process, specific compounds help digest and absorb the nutrients in foods. These compounds known as enzymes break down fats, proteins, and carbohydrates in foods [R]. 

Different Types of Enzymes

Natural digestive enzymes are found in the gastrointestinal tract. Here is a list of digestive enzymes [R]: 


  • Amylase
  • Protease
  • Lipase
  • Other types of digestive enzymes 

Amylase

Amylase is an enzyme that breaks down carbohydrates. It converts carbs into simple sugars. Amylase is made by the saliva and pancreas. It is found in the mouth and small intestine [R].

Protease

Enzymes for digestion of protein are known as proteases. A protease is an enzyme that breaks down protein into different amino acids. These compounds are used for several body functions including renewal and repair of cells. Enzymes for proteins include [R,R]:


  • Pepsin
  • Trypsin
  • Chymotrypsin

Pepsin is found in stomach acid. Trypsin and chymotrypsin are made by the pancreas. During digestion these enzymes are secreted into the small intestine [R].

Lipase

Lipase is an enzyme that breaks down fats and oils. They are made and secreted by the pancreas. Lipase is found in the liver, fat cells, veins, arteries, and the small intestine [R].

Other types of Digestive Enzymes

Other types of enzymes include lactase, alpha-galactosidase, phytase, and cellulase. 


Lactase is an enzyme that breaks down lactose. This is a sugar found in dairy products. Lactase is found in the small intestine. [R]. 


Alpha-galactosidase is an enzyme that breaks down complex carbohydrates like beans and peas [R]. Phytase is an enzyme that breaks down grains and seed oil [R]. These enzymes are found in the small intestine [R, R]. 


Cellulase is an enzyme found only in vegetables. It breaks down a plant’s cellulose or fiber into a beta-glucose. Beta-glucose is a type of carb found in plants [R, R]. The breakdown of cellulose in humans varies depending on the gut bacteria present [R]. 


These enzymes have also been made into dietary supplements. These are derived from both animal and plant sources and contain a combination of lipase, amylase, proteases, and/or other enzymes [R, R].  

Benefits of Digestive Enzymes

The benefits of digestive enzymes include better digestion, improved gut health, weight loss, reducing muscle soreness and treating health conditions.

Enzymes for Improved Digestion

Regularity, as well as a decrease in gas, bloating, and stomach pain have been seen with the use of digestive enzymes [R, R]. The use of two or more enzymes was also effective in combating fullness, nausea, heartburn, regurgitation, burping, and/or lack of appetite [R]. 

Digestive Enzymes for Leaky Gut

Digestive enzymes may also heal leaky gut. These compounds were able to increase the bacteria diversity in the gut [R. Mice given lipase had an increase in the level of Lactobacillus reuteri, an anti-inflammatory bacteria known for relieving intestinal inflammation [R]. 

Enzymes for Weight Loss

A healthy gut is also needed for weight loss [R]. 

So the more healthy bacteria present the more likely you are to lose weight [R. If these compounds can increase the presence of healthy gut bacteria there is the potential to use enzymes for weight loss.


Alternatively, digestive enzyme inhibitors have been successful for weight loss. These supplements will prevent enzymes from working and reduce the amount of nutrients absorbed [R]. 


The use of lipase, amylase, and trypsin blockers caused reductions in the absorption of fat, carbs, and protein. Reductions in both fat and weight loss were seen with the use of these supplements [R, R, R]. 

Enzymes for Muscle Soreness

Protease enzymes may also improve muscle soreness. Protease tablets reduce muscle soreness when used before and during exercise. 


Runners who took 8 protease tablets containing  325 mg pancreatic enzymes, 75 mg trypsin, 50 mg papain, 50 mg bromelain, 10 mg amylase, 10 mg lipase, 10 mg lysozyme, and 2 mg chymotrypsin had better muscle healing and contraction of their leg muscles than those who took a placebo over the course of 4 days [R]. 

Enzymes for Health Conditions

Digestive enzymes have been successful in treating malabsorption and digestive disorders including diabetes, lactose intolerance, and pancreas disorders like chronic pancreatitis [R]. 

When to Take Digestive Enzymes

Some individuals have malabsorption and digestive disorders that cause a lack of enzymes. As a result, their digestion may be compromised and digestive enzyme supplements may be recommended [R].  


If you find yourself with gas, bloating, stomach pain and fullness after eating you may also benefit from digestive enzyme supplementation  [R].


Supplements to help digestion may also provide some relief for muscle soreness as noted above.

What to Look for in a Digestive Enzyme

The potency of the enzyme depends on how it is made [R]. Animal and plant-based digestive enzymes are available. Enzymes derived from animals like pork and cows are typically used to make digestive enzymes. How well this type of enzyme works depends on the age, species, sex, and breeding of the animal [R].


Pork enzymes are similar to humans. They are about 30 to 50 percent more effective than beef sources. However, enzymes made from plants and microbes also produced positive results. Their popularity is growing. They also provide a solution for people who are vegetarian and vegan [R]. 


Digestive enzyme supplements are not regulated. So the amount and activity can vary by brand [R, R]. When choosing a digestive enzyme look for one that is third-party testing for quality

[R].

Digestive Enzymes Dosage Recommendations

There is no standard dosage for digestive enzymes. So it usually varies from brand to brand. It is best to start with a low dose and follow the manufacturer's instructions. Start with a short trial for just two or three weeks to see how they affect you [R]. 

Are Digestive Enzymes Safe

Since digestive enzymes are not regulated the doses can be all over the place. Some products have unclear and misleading labels [R]. This means you may not be getting what is advertised on the box.  


Some research has shown digestive enzymes may be proinflammatory. Cells treated with amylase and the proteases bromelain and papain caused the production cells seen with inflammation and viral infections [R,  

R, R]. 


Lipase inhibitors can increase hunger, diarrhea and stomach pain [R R]. On the other hand, the use of the lipase causes hunger when eaten with a fat meal. This could lead to excess food intake and possible weight gain [R]. 


Overall, digestive enzymes seem to be generally safe when following the manufacturers directions. There have been side effects seen with the use of this supplement. They include stomach pain, nausea, and diarrhea. Allergic reactions, stomach blockages, gallstones, high uric acid, itching, hives, and rash are more rare side effects [R].


More research needs to be done to know the true negative effects of digestive enzymes. So those with health conditions and/or on medications should check with their healthcare professional before starting these supplements.

Foods with Digestive Enzymes

An alternative to taking digestive enzyme supplements is adding foods with high enzymes to the diet. Foods with digestive enzymes that occur in them naturally include the following: 


  • Pineapple [R
  • Papaya [R
  • Mango [R
  • Honey [R, R, R, R, R
  • Bananas [R
  • Avocados [R, R]  
  • Kefir [R, R, R
  • Sauerkraut [R
  • Kimchi [R, R
  • Miso [R, R, R]  
  • Kiwifruit [R, R
  • Ginger [R

Lipase in foods consists of avocados, kefir, kimchi, and miso [R, R, R, R, R, R, R, R]. Amylase enzymes were found in mangoes, bananas, kimchi, and miso [R, R, R, R, R, R]. Proteases are found in papaya and ginger [R, R]. Raw honey contains both amylase and protease enzymes Honey [R, R, R, R, R]. Kefir, kimchi, and miso contain all three types of enzymes [R, R, R, R, R, R, R, R]. 

What are Probiotics

Probiotics consist of live strains of bacteria and yeast. These microorganisms are found in fermented foods, added to foods during processing, and are made into dietary supplements [R]. 


Common strains of bacteria include Lactobacillus and Bifidobacterium. Yeast found in probiotics are Saccharomyces boulardii [R]. 

Prebiotic v. Probiotic

Probiotics are not to be confused with prebiotics. Prebiotics are microbes while prebiotics are the by-product of fiber digestion. These substances produce substances that promote the growth of healthy bacteria [R]. 


Prebiotics are created when foods with fiber are digested.

What Do Probiotics Help With

The health benefits of probiotics include  improved digestion, cholesterol, immune function, metabolism and weight loss. 

Probiotics for Digestive Health

Probiotics support a healthy gut and digestive system. The gastrointestinal system is lined with bacteria, virus, fungi, protozoa and other microbes [R]. 


These organisms have positive effects on digestive health. They increase the production of healthy bacteria and cultivate a healthy microbiome. A healthy gut will also support digestion. Probiotics also can prevent the growth of harmful bacteria, increase nutrient absorption, improve transit time of foods, and produce compounds that feed healthy bacteria such as short-chain fatty acids [R].


Lactobacillus probiotics can reduce stomach pain and diarrhea. Lactobacillus rhamnosus GG and Saccharomyces boulardii can stop diarrhea resulting from antibiotics. Lactobacillus, Saccharomyces boulardii, and Bifidobacterium lactis are helpful for constipation 

[R, R, R, R R, R].  


The best probiotics for digestive health seem to come from the Lactobacillus and Bifidobacterium families [R]. This could also be due to the fact these are the most widely researched probiotic strains. Little is known about how other probiotics affect digestion.

Probiotics for Cholesterol

Certain probiotics may reduce “bad” LDL and total cholesterol levels better than a placebo. The use of Lactobacillus acidophilus, Lactobacillus plantarum and a mixture of Lactobacillus acidophilus and Bifidobacterium lactis was the most effective on cholesterol levels when taken over a period of three to 12 weeks [R]. 


People with normal or high cholesterol levels also saw reductions in their LDL and total cholesterol after taking Lactobacillus acidophilus for 4 weeks or more. Those with mild cholesterol had greater reductions than those with normal levels [R]. 

Probiotics for Immune Health

Probiotics prevent the growth of harmful bacteria in the gut. This can help improve function of the immune system [R


Immune responses were increased by the presence of Lactobacillus. Pathogen destroying immune cells and antibodies formed after taking this probiotic [R]. 


Other research shows a reduction in respiratory and urinary tract infections among those taking this type of probiotic [R, R]

Probiotics for Metabolism and Weight Loss

Probiotics may provide a healthy microbiome that is needed for improved metabolism and weight loss [R]. However, research on probiotics and weight loss is conflicting.


Lactobacillus and Bifidobacterium strains of probiotics have been associated with fat reduction and weight loss [R, R, R, R]. 


Multi-strain probiotics were also effective at preventing weight gain when compared with a placebo. A small study of non obese men gained less body fat and weight after taking VSL#3 when consuming a high calorie high fat diet for four weeks [R]. 


On the other hand, weight gain was also associated with the use of probiotics. Lactobacillus acidophilus, was found to increase weight [R].


While there are promising results. When it comes to dosage, duration, and long-term effects for weight loss more research needs to be done to know the true effects of probiotics before they can be used as weight loss treatment [R, R].

When to Take Probiotics 

If you do not like fermented foods a supplement may be beneficial to increase your intake of probiotics [R].


Probiotic supplements have also been recommended for certain health conditions including stomach pain, diarrhea, and constipation [R, R, R, R].  


However, if you have a health condition and/or are on any medications it is best to ask a health professional about the best probiotics before starting any supplements.

What to Look for in a Probiotic

As with other supplements, probiotics are not regulated. To ensure a quality product look for tablets, microcapsules, and bead probiotics with at least 1 billion colony forming units (CFUs), a coating to withstand stomach acid, and is third party tested for purity [R].

Probiotic Supplement Dosages 

Overall, research on probiotics is still ongoing so there is no specific dosage recommendation.


Some evidence shows the chance of survival of certain probiotics was better with foods than with juice or water [R]. The presence of fat, sugar and/or carbs may also help bacteria survive digestion [R, R].


Some probiotics need to be taken before a meal, while others live on without being combined with food  [R, R].


Consistency of use seems to be most important for health benefits [R]. So be sure to follow the directions on the label.

Are Probiotics Safe

For the most part probiotics seem to be safe when using them for 9 months up to a year. There have also been side effects associated with these supplements. Gas and bloating are commonly seen with the use of Lactobacillus, Bifidobacteria, Streptococcus thermophilus, and Saccharomyces boulardii. The negative effects of other types of probiotics are unknown [R]. 


Other concerns include interactions with medications and the potential for intestinal bacterial overgrowth and antibiotic resistance. It could lead people susceptible to infection from pathogens. This can be very dangerous for people with poor immune function [R, R, R, R]. 


Those with a compromised immune function, other health conditions, and/or are on medications should ask their healthcare provider before taking probiotics. More research needs to be done to show the true risks of these supplements. [R].

Foods with Probiotics

There are also foods that naturally contain probiotics. Live bacteria and yeast can be found in fermented foods such as  apple cider vinegar, cheese, kimchi, kombucha, miso, and sauerkraut. [R]. 


Some foods have microorganisms added to them during processing. These include yogurt, milks, juices, smoothies, cereals, and nutrition bars [R]. 


Sourdough bread and pickles are foods that naturally contain live cultures but are killed during food processing [R]. Alternatively raw fermented foods like pickles will still contain the live probiotics. However, raw foods do have  a chance of causing a foodborne illness [R].

Digestive Enzyme vs. Probiotic

Probiotics are found in foods and supplements while enzymes are made by the body. 

[R]. The jobs of probiotics and digestive enzymes also vary. Probiotics provide healthy bacteria while enzymes increase ease digestion. 

Probiotics and  Digestive Enzymes Work Well Together

No need to worry about taking these products together. In animals, the combination of probiotics and digestive enzymes actually enhanced nutrient absorption and improved the microbiome [R].


There are also probiotic enzymes available on the market. These have been effective at lowering LDL and increasing “good” HDL cholesterol in animals [R]. 


Using probiotics with enzymes was helpful in treating lactose intolerance, pancreas disorders, muscle soreness, and medication-induced gut inflammation [R, R, R].


The fungus Aspergillusoryzae can survive stomach acid and will find its way to the small intestine. Digestive enzymes paired with this microbe reduced muscle soreness. It is also being researched as a potential treatment for celiac disease [R, R].


​​Depending on the instructions on the box you may be able to take probiotics and digestive enzymes at the same time.

Summary

A healthy gut and digestive tract is key to a good well-being. Probiotics and digestive enzymes have the ability to stimulate positive bacterial growth and break down food particles. As supplements they have been shown to improve digestion, gut health, immune function, cholesterol, weight loss, and muscle soreness.

Probiotics and digestive enzymes have also been used to treat stomach pain, constipation, diarrhea, diabetes, lactose intolerance, and pancreas disorders.


Unfortunately, there are no regulations on these products so it is hard to know what are the best digestive supplements and probiotics out there. There are also some concerns over the safety of these products. Some seem harmless with a few side effects. However, research is limited and there is still a lot we don’t know about probiotics and digestive enzymes.


If you have a health condition and/or are on medication you should check with a healthcare professional to know if these supplements are right for you.  In the meantime you can also find certain foods that already contain these compounds. Eating foods like pineapple, papaya, honey, avocados, kimchi, miso, kiwifruit, ginger, yogurt, and pickles can naturally boost your levels of  probiotics and digestive enzymes.


Resources

  1. Ianiro G, Pecere S, Giorgio V, Gasbarrini A, Cammarota G. Digestive Enzyme Supplementation in Gastrointestinal Diseases. Curr Drug Metab. 2016;17(2):187-193. doi:10.2174/138920021702160114150137 
  2. Akinfemiwa O, Muniraj T. Amylase. In: StatPearls. StatPearls Publishing; 2021.
  3. Bond JS. Proteases: History, discovery, and roles in health and disease. J Biol Chem. 2019;294(5):1643-1651. doi:10.1074/jbc.TM118.004156
  4. Amino acids: MedlinePlus Medical Encyclopedia.
  5. Pirahanchi Y, Sharma S. Biochemistry, Lipase. In: StatPearls. StatPearls Publishing; 2021. 
  6. The Editors of Encyclopedia Britannica. Lactase. In: Encyclopedia Britannica. ; 2020.
  7. GLA gene:  MedlinePlus Medical Encyclopedia.
  8. Mullaney EJ, Daly CB, Ullah AHJ. Advances in Phytase Research.; 2000.
  9. LeBlanc JG, Piard J-C, Sesma F, de Giori GS. Lactobacillus fermentum CRL 722 is able to deliver active alpha-galactosidase activity in the small intestine of rats. FEMS Microbiol Lett. 2005;248(2):177-182. doi:10.1016/j.femsle.2005.05.054
  10. Iqbal TH, Lewis KO, Cooper BT. Phytase activity in the human and rat small intestine. Gut. 1994;35(9):1233-1236. doi:10.1136/gut.35.9.1233
  11. Jayasekara S, Ratnayake R. Microbial Cellulases: An Overview and Applications. In: Pascual AR, Martín MEE, eds. Cellulose. IntechOpen; 2019. doi:10.5772/intechopen.84531
  12. PubChem. beta-D-Glucose
  13. Chassard C, Delmas E, Robert C, Bernalier-Donadille A. The cellulose-degrading microbial community of the human gut varies according to the presence or absence of methanogens. FEMS Microbiol Ecol. 2010;74(1):205-213. doi:10.1111/j.1574-6941.2010.00941.x
  14. Pierzynowska K, Valverde-Piedra J, Szymanczyk S, et al. Pancreatic-like enzymes of microbial origin restore growth and normalize lipid absorption in a pig model with exocrine pancreatic insufficiency. Arch Med Sci. 2018;14(2):407-414. doi:10.5114/aoms.2018.73471
  15. Roxas M. The role of enzyme supplementation in digestive disorders. Altern Med Rev. 2008;13(4):307-314.
  16. Money ME, Walkowiak J, Virgilio C, Talley NJ. Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome-diarrhoea. Frontline Gastroenterol. 2011;2(1):48-56. doi:10.1136/fg.2010.002253
  17. Ciacci C, Franceschi F, Purchiaroni F, et al. Effect of beta-glucan, inositol and digestive enzymes in GI symptoms of patients with IBS. Eur Rev Med Pharmacol Sci. 2011;15(6):637-643. 
  18. Majeed M, Majeed S, Nagabhushanam K, et al. Evaluation of the Safety and Efficacy of a Multienzyme Complex in Patients with Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled Study. J Med Food. 2018;21(11):1120-1128. doi:10.1089/jmf.2017.4172
  19. Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019;11(7). doi:10.3390/nu11071613
  20. Nishiyama H, Nagai T, Kudo M, et al. Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice. Biochem Biophys Res Commun. 2018;495(1):273-279. doi:10.1016/j.bbrc.2017.10.130
  21. Castaner O, Goday A, Park Y-M, et al. The Gut Microbiome Profile in Obesity: A Systematic Review. Int J Endocrinol. 2018;2018:4095789. doi:10.1155/2018/4095789
  22. John GK, Wang L, Nanavati J, Twose C, Singh R, Mullin G. Dietary Alteration of the Gut Microbiome and Its Impact on Weight and Fat Mass: A Systematic Review and Meta-Analysis. Genes . 2018;9(3). doi:10.3390/genes9030167
  23. Tucci SA, Boyland EJ, Halford JC. The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents. Diabetes Metab Syndr Obes. 2010;3:125-143. doi:10.2147/dmsott.s7005
  24. Udani J, Tan O, Molina J. Systematic Review and Meta-Analysis of a Proprietary Alpha-Amylase Inhibitor from White Bean (Phaseolus vulgaris L.) on Weight and Fat Loss in Humans. Foods. 2018;7(4). doi:10.3390/foods7040063
  25. Ribeiro JA do NC, Serquiz AC, Silva PF dos S, et al. Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels. Clinics . 2015;70(2):136-143. doi:10.6061/clinics/2015(02)11 
  26. Miller PC, Bailey SP, Barnes ME, Derr SJ, Hall EE. The effects of protease supplementation on skeletal muscle function and DOMS following downhill running. J Sports Sci. 2004;22(4):365-372. doi:10.1080/02640410310001641584 
  27. Edakkanambeth Varayil J, Bauer BA, Hurt RT. Over-the-counter enzyme supplements: what a clinician needs to know. Mayo Clin Proc. 2014;89(9):1307-1312. doi:10.1016/j.mayocp.2014.05.015 
  28. Robinson PK. Enzymes: principles and biotechnological applications. Essays Biochem. 2015;59:1-41. doi:10.1042/bse0590001
  29. ConsumerLab. Tests and Compares Digestive Enzyme Supplements.
  30. Zhang F, Si M, Wang H, Mekhemar MK, Dörfer CE, Fawzy El-Sayed KM. IL-1/TNF-α Inflammatory and Anti-Inflammatory Synchronization Affects Gingival Stem/Progenitor Cells’ Regenerative Attributes. Stem Cells Int. 2017;2017:1349481. doi:10.1155/2017/1349481
  31. Alpha Interferon. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2018. 
  32. Bansal AB, Al Khalili Y. Orlistat. In: StatPearls. StatPearls Publishing; 2020. 
  33. Seyedan A, Alshawsh MA, Alshagga MA, Koosha S, Mohamed Z. Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review. Evid Based Complement Alternat Med. 2015;2015:973143. doi:10.1155/2015/973143
  34. Levine ME, Koch SY, Koch KL. Lipase Supplementation before a High-Fat Meal Reduces Perceptions of Fullness in Healthy Subjects. Gut Liver. 2015;9(4):464-469. doi:10.5009/gnl14005
  35. Digestive Enzymes Combination No.7 Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD.
  36. Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int. 2012;2012:976203. doi:10.1155/2012/976203
  37. Stremnitzer C, Manzano-Szalai K, Willensdorfer A, et al. Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation. J Invest Dermatol. 2015;135(7):1790-1800. doi:10.1038/jid.2015.58
  38. Peroni FHG, Koike C, Louro RP, et al. Mango starch degradation. II. The binding of alpha-amylase and beta-amylase to the starch granule. J Agric Food Chem. 2008;56(16):7416-7421. doi:10.1021/jf800469w 
  39. Burlando B, Cornara L. Honey in dermatology and skin care: a review. J Cosmet Dermatol. 2013;12(4):306-313. doi:10.1111/jocd.12058
  40. Sakač N, Sak-Bosnar M. A rapid method for the determination of honey diastase activity. Talanta. 2012;93:135-138. doi:10.1016/j.talanta.2012.01.063 
  41. Babacan S, Rand AG. Characterization of honey amylase. J Food Sci. 2007;72(1):C050-C055. doi:10.1111/j.1750-3841.2006.00215.x 
  42. Sánchez MP, Huidobro JF, Mato I, Muniategui S, Sancho MT. Evolution of invertase activity in honey over two years. J Agric Food Chem. 2001;49(1):416-422. doi:10.1021/jf0003350
  43. Rossano R, Larocca M, Polito T, et al. What are the proteolytic enzymes of honey and what they do tell us? A fingerprint analysis by 2-D zymography of unifloral honeys. PLoS One. 2012;7(11):e49164. doi:10.1371/journal.pone.0049164 
  44. Bassinello PZ, Cordenunsi BR, Lajolo FM. Amylolytic activity in fruits: comparison of different substrates and methods using banana as model. J Agric Food Chem. 2002;50(21):5781-5786. doi:10.1021/jf011370p
  45. Tursi JM, Phair PG, Barnes GL. Plant sources of acid stable lipases: potential therapy for cystic fibrosis. J Paediatr Child Health. 1994;30(6):539-543. doi:10.1111/j.1440-1754.1994.tb00730.x
  46. Kahn V. Polyphenol oxidase activity and browning of three avocado varieties. J Sci Food Agric. 1975;26(9):1319-1324. doi:10.1002/jsfa.2740260910
  47. Ebner J, Aşçı Arslan A, Fedorova M, Hoffmann R, Küçükçetin A, Pischetsrieder M. Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains. J Proteomics. 2015;117:41-57. doi:10.1016/j.jprot.2015.01.005
  48. Magalhães KT, Pereira GV de M, Campos CR, Dragone G, Schwan RF. Brazilian kefir: structure, microbial communities and chemical composition. Braz J Microbiol. 2011;42(2):693-702. doi:10.1590/S1517-83822011000200034
  49. de Oliveira Leite AM, Miguel MAL, Peixoto RS, Rosado AS, Silva JT, Paschoalin VMF. Microbiological, technological and therapeutic properties of kefir: a natural probiotic beverage. Braz J Microbiol. 2013;44(2):341-349. doi:10.1590/S1517-83822013000200001
  50. Swain MR, Anandharaj M, Ray RC, Parveen Rani R. Fermented fruits and vegetables of Asia: a potential source of probiotics. Biotechnol Res Int. 2014;2014:250424. doi:10.1155/2014/250424 
  51. Wang Y, Wu Y, Wang Y, et al. Antioxidant Properties of Probiotic Bacteria. Nutrients. 2017;9(5). doi:10.3390/nu9050521
  52. Ikram-Ul-Haq, Mukhtar H. Protease biosynthesis from Lactobacillus species: Fermentation parameters and kinetics. J Food Process Preserv. 2007;31(1):102-115. doi:10.1111/j.1745-4549.2007.00111.x
  53. Chancharoonpong C, Hsieh P-C, Sheu S-C. Enzyme Production and Growth of Aspergillus oryzae S. on Soybean Koji Fermentation. APCBEE Procedia. 2012;2:57-61. doi:10.1016/j.apcbee.2012.06.011
  54. Toida J, Kondoh K, Fukuzawa M, Ohnishi K, Sekiguchi J. Purification and characterization of a lipase from Aspergillus oryzae. Biosci Biotechnol Biochem. 1995;59(7):1199-1203. doi:10.1271/bbb.59.1199 
  55. Zhao Q, Liu F, Hou Z, Yuan C, Zhu X. High level production of β-galactosidase exhibiting excellent milk-lactose degradation ability from Aspergillus oryzae by codon and fermentation optimization. Appl Biochem Biotechnol. 2014;172(6):2787-2799. doi:10.1007/s12010-013-0684-2
  56. Sugiyama S, Hirota A, Okada C, Yorita T, Sato K, Ohtsuki K. Effect of kiwifruit juice on beef collagen. J Nutr Sci Vitaminol . 2005;51(1):27-33. doi:10.3177/jnsv.51.27
  57. Boland M. Kiwifruit proteins and enzymes: actinidin and other significant proteins. Adv Food Nutr Res. 2013;68:59-80. doi:10.1016/B978-0-12-394294-4.00004-3 
  58. Huang XW, Chen LJ, Luo YB, Guo HY, Ren FZ. Purification, characterization, and milk coagulating properties of ginger proteases. J Dairy Sci. 2011;94(5):2259-2269. doi:10.3168/jds.2010-4024
  59. Fact Sheet for Consumers. Probiotics. Dent Abstr. 2010;55(3):162-164. doi:10.1016/j.denabs.2009.12.034
  60. National Center for Complementary and Integrative Health (NIH). Probiotics: What you need to know
  61. Zmora N, Zilberman-Schapira G, Suez J, et al. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell. 2018;174(6):1388-1405.e21. doi:10.1016/j.cell.2018.08.041 
  62. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. doi:10.1038/nrgastro.2014.66
  63. Aragon G, Graham DB, Borum M, Doman DB. Probiotic therapy for irritable bowel syndrome. Gastroenterol Hepatol . 2010;6(1):39-44.
  64. Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Outpatients-A Systematic Review and Meta-Analysis. Antibiotics (Basel). 2017;6(4). doi:10.3390/antibiotics6040021
  65. Gomes DOVS, Morais MB de. GUT MICROBIOTA AND THE USE OF PROBIOTICS IN CONSTIPATION IN CHILDREN AND ADOLESCENTS: SYSTEMATIC REVIEW. Rev Paul Pediatr. 2020;38:e2018123. doi:10.1590/1984-0462/2020/38/2018123 
  66. Terciolo C, Dapoigny M, Andre F. Beneficial effects of Saccharomyces boulardii CNCM I-745 on clinical disorders associated with intestinal barrier disruption. Clin Exp Gastroenterol. 2019;12:67-82. doi:10.2147/CEG.S181590
  67. Chmielewska A, Szajewska H. Systematic review of randomised controlled trials: probiotics for functional constipation. World J Gastroenterol. 2010;16(1):69-75. doi:10.3748/wjg.v16.i1.69
  68. Cho YA, Kim J. Effect of Probiotics on Blood Lipid Concentrations: A Meta-Analysis of Randomized Controlled Trials. Medicine . 2015;94(43):e1714. doi:10.1097/MD.0000000000001714
  69. Shimizu M, Hashiguchi M, Shiga T, Tamura H-O, Mochizuki M. Meta-Analysis: Effects of Probiotic Supplementation on Lipid Profiles in Normal to Mildly Hypercholesterolemic Individuals. PLoS One. 2015;10(10):e0139795. doi:10.1371/journal.pone.0139795
  70. Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut. 2003;52(7):988-997. doi:10.1136/gut.52.7.988
  71. Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev. 2003;16(4):658-672. doi:10.1128/CMR.16.4.658-672.2003
  72. Hatakka K, Savilahti E, Pönkä A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;322(7298):1327. doi:10.1136/bmj.322.7298.1327
  73. Stapleton AE, Au-Yeung M, Hooton TM, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011;52(10):1212-1217. doi:10.1093/cid/cir183
  74. Angelakis E, Merhej V, Raoult D. Related actions of probiotics and antibiotics on gut microbiota and weight modification. Lancet Infect Dis. 2013;13(10):889-899. doi:10.1016/S1473-3099(13)70179-8
  75. Libby J, Martinez R, Weber MJ. Tyrosine phosphorylation in cells treated with transforming growth factor-beta. J Cell Physiol. 1986;129(2):159-166. doi:10.1002/jcp.1041290206
  76. Kadooka Y, Sato M, Ogawa A, et al. Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. Br J Nutr. 2013;110(9):1696-1703. doi:10.1017/S0007114513001037
  77. Wang Z-B, Xin S-S, Ding L-N, et al. The Potential Role of Probiotics in Controlling Overweight/Obesity and Associated Metabolic Parameters in Adults: A Systematic Review and Meta-Analysis. Evid Based Complement Alternat Med. 2019;2019:3862971. doi:10.1155/2019/3862971
  78. Brusaferro A, Cozzali R, Orabona C, et al. Is It Time to Use Probiotics to Prevent or Treat Obesity? Nutrients. 2018;10(11). doi:10.3390/nu10111613
  79. Osterberg KL, Boutagy NE, McMillan RP, et al. Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults. Obesity . 2015;23(12):2364-2370. doi:10.1002/oby.21230
  80. Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D. Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb Pathog. 2012;53(2):100-108. doi:10.1016/j.micpath.2012.05.007
  81. Park S, Bae J-H. Probiotics for weight loss: a systematic review and meta-analysis. Nutr Res. 2015;35(7):566-575. doi:10.1016/j.nutres.2015.05.008
  82. Marco ML, Heeney D, Binda S, et al. Health benefits of fermented foods: microbiota and beyond. Curr Opin Biotechnol. 2017;44:94-102. doi:10.1016/j.copbio.2016.11.010
  83. Govender M, Choonara YE, Kumar P, du Toit LC, van Vuuren S, Pillay V. A review of the advancements in probiotic delivery: Conventional vs. non-conventional formulations for intestinal flora supplementation. AAPS PharmSciTech. 2014;15(1):29-43. doi:10.1208/s12249-013-0027-1
  84. Tompkins TA, Mainville I, Arcand Y. The impact of meals on a probiotic during transit through a model of the human upper gastrointestinal tract. Benef Microbes. 2011;2(4):295-303. doi:10.3920/BM2011.0022
  85. Corcoran BM, Stanton C, Fitzgerald GF, Ross RP. Survival of probiotic lactobacilli in acidic environments is enhanced in the presence of metabolizable sugars. Appl Environ Microbiol. 2005;71(6):3060-3067. doi:10.1128/AEM.71.6.3060-3067.2005
  86. Toscano M, De Grandi R, Stronati L, De Vecchi E, Drago L. Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: A preliminary study. World J Gastroenterol. 2017;23(15):2696-2704. doi:10.3748/wjg.v23.i15.2696
  87. Williams NT. Probiotics. Am J Health Syst Pharm. 2010;67(6):449-458. doi:10.2146/ajhp090168
  88. Walsh J, Griffin BT, Clarke G, Hyland NP. Drug-gut microbiota interactions: implications for neuropharmacology. Br J Pharmacol. 2018;175(24):4415-4429. doi:10.1111/bph.14366
  89. Kothari D, Patel S, Kim S-K. Probiotic supplements might not be universally-effective and safe: A review. Biomed Pharmacother. 2019;111:537-547. doi:10.1016/j.biopha.2018.12.104
  90. Lerner A, Shoenfeld Y, Matthias T. Probiotics: If It Does Not Help It Does Not Do Any Harm. Really? Microorganisms. 2019;7(4). doi:10.3390/microorganisms7040104
  91. Zheng M, Zhang R, Tian X, Zhou X, Pan X, Wong A. Assessing the Risk of Probiotic Dietary Supplements in the Context of Antibiotic Resistance. Front Microbiol. 2017;8:908. doi:10.3389/fmicb.2017.00908
  92. Health Professional Fact Sheet. Probiotics. Dent Abstr. 2010;55(3):162-164. doi:10.1016/j.denabs.2009.12.034
  93. Behera SS, El Sheikha AF, Hammami R, Kumar A. Traditionally fermented pickles: How the microbial diversity associated with their nutritional and health benefits? J Funct Foods. 2020;70:103971. doi:10.1016/j.jff.2020.103971
  94. Maas RM, Deng Y, Dersjant-Li Y, et al. Exogenous enzymes and probiotics alter digestion kinetics, volatile fatty acid content and microbial interactions in the gut of Nile tilapia. Sci Rep. 2021;11(1):8221. doi:10.1038/s41598-021-87408-3
  95. Ichim TE, Patel AN, Shafer KA. Experimental support for the effects of a probiotic/digestive enzyme supplement on serum cholesterol concentrations and the intestinal microbiome. J Transl Med. 2016;14(1):184. doi:10.1186/s12967-016-0945-2
  96. Multi − Enzyme Complex for the Management of Delayed Onset Muscle Soreness after Eccentric Exercise : A Randomized , Double Blind , Placebo Controlled Study. Published online 2016. 
  97. Ichim TE, Kesari S, Shafer K. Protection from chemotherapy- and antibiotic-mediated dysbiosis of the gut microbiota by a probiotic with digestive enzymes supplement. Oncotarget. 2018;9(56):30919-30935. doi:10.18632/oncotarget.25778