Understanding mode of action can drive the translational pipeline towards more reliable health benefits for probiotics

Current Opinion in Biotechnology

Volumn 56, Issue , 2019, Pages 55-60

  Kleerebezem, Michiel ^a   Binda, Sylvie ^b   Bron, Peter A ^c   Gross, Gabriele ^d   Hill, Colin ^e   van Hylckama Vlieg, Johan ET ^f   Lebeer, Sarah ^g   Satokari, Reetta ^h   Ouwehand, Arthur C ⁱ  

^a WAGENINGEN UNIVERSITY   (Netherlands)

^b Groupe Danone   (France)

^c BE Basic Foundation   (Netherlands)

^d RECKITT BENCKISER   (United Kingdom)

^e UNIVERSITY COLLEGE CORK   (Ireland)

^f CHR HANSEN A S   (Denmark)

^g UNIVERSITY OF ANTWERP   (Belgium)

^h UNIVERSITY OF HELSINKI   (Finland)

ⁱ DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PIPELINES;

CLINICAL TRIAL; HEALTH BENEFITS; HUMAN HEALTH; HUMAN HEALTH EFFECTS; MODE OF ACTION; MOLECULAR MECHANISM; PRE-CLINICAL; PROBIOTIC PRODUCTS;

HEALTH;

BACTERIOCIN; EPIDERMAL GROWTH FACTOR RECEPTOR; LACTOSE; PROBIOTIC AGENT; YOGHURT;

ANTIBIOTIC ASSOCIATED DIARRHEA; CLINICAL EFFECTIVENESS; DIGESTIVE SYSTEM FUNCTION DISORDER; HUMAN; LACTOBACILLUS DELBRUECKII SUBSP. BULGARICUS; LACTOBACILLUS RHAMNOSUS; MICROBIAL ACTIVITY; NECROTIZING ENTEROCOLITIS; NONHUMAN; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; PROTEIN SECRETION; REVIEW; STREPTOCOCCUS THERMOPHILUS; TREATMENT OUTCOME; TREATMENT RESPONSE; ANIMAL; INTESTINE FLORA; METABOLISM; MICROBIOLOGY; TRANSLATIONAL RESEARCH;

ANIMALS; GASTROINTESTINAL MICROBIOME; HUMANS; LACTOSE; PROBIOTICS; TRANSLATIONAL MEDICAL RESEARCH; YOGURT;

EID: 85054246168     PISSN: 09581669     EISSN: 18790429     Source Type: Journal    
DOI: 10.1016/j.copbio.2018.09.007     Document Type: Review

References (48)

1. http://www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf.
2. Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B., Morelli, L., Canani, R.B., Flint, H.J., Salminen, S., 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 11 (2014), 506–514 Important conceptual paper, that recognizes that certain health benefits depend on core properties that are conserved in different probiotics, while other benefits may be more species or strain specific. See also reference 14 for an expanded description of these core properties.
3. Panigrahi, P., Parida, S., Nanda, N.C., Satpathy, R., Pradhan, L., Chandel, D.S., Baccaglini, L., Mohapatra, A., Mohapatra, S.S., Misra, P.R., et al. A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature 548 (2017), 407–412 Landmark study that describes the remarkable protection by a synbiotic product against sepsis and death (40% reduction) in a large infant cohort (4556 infants) in rural India, although the study did not disentangle the relative contribution of the probioticLactobacillus plantarum and the fructooligosaccharides to the observed effect.
4. Ritchie, M.L., Romanuk, T.N., A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One, 7, 2012, e34938.
5. Parker, E.A., Roy, T., D'Adamo, C.R., Wieland, L.S., Probiotics and gastrointestinal conditions: an overview of evidence from the Cochrane collaboration. Nutrition 45 (2018), 125–134 e111.
6. Lebeer, S., Bron, P.A., Marco, M.L., Van Pijkeren, J.P., O'Connell Motherway, M., Hill, C., Pot, B., Roos, S., Klaenhammer, T., Identification of probiotic effector molecules: present state and future perspectives. Curr Opin Biotechnol 49 (2018), 217–223.
7. Maldonado-Gomez, M.X., Martinez, I., Bottacini, F., O'Callaghan, A., Ventura, M., van Sinderen, D., Hillmann, B., Vangay, P., Knights, D., Hutkins, R.W., et al. Stable engraftment of Bifidobacterium longum AH1206 in the Human gut depends on individualized features of the resident microbiome. Cell Host Microbe 20 (2016), 515–526 This study demonstrates that the engraftment of aBifidobacterium longum strain can be predicted on basis of metagenomic characterization of the intestinal microbiome of the individual to which the strain is administered, thereby illustrating how molecular stratification can be employed to predict efficacy, in this case of colonization.
8. Derrien, M., van Hylckama Vlieg, J.E., Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol 23 (2015), 354–366.
9. Kristensen, N.B., Bryrup, T., Allin, K.H., Nielsen, T., Hansen, T.H., Pedersen, O., Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med, 8, 2016, 52.
10. Marteau, P., Flourie, B., Pochart, P., Chastang, C., Desjeux, J.F., Rambaud, J.C., Effect of the microbial lactase (EC 3.2.1.23) activity in yoghurt on the intestinal absorption of lactose: an in vivo study in lactase-deficient humans. Br J Nutr 64 (1990), 71–79.
11. EFSA Panel on Dietetic Products NaA, Scientific opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 8 (2010), 1763–1781.
12. Bonder, M.J., Kurilshikov, A., Tigchelaar, E.F., Mujagic, Z., Imhann, F., Vila, A.V., Deelen, P., Vatanen, T., Schirmer, M., Smeekens, S.P., et al. The effect of host genetics on the gut microbiome. Nat Genet 48 (2016), 1407–1412 This study not only confirmed the association between the abundance ofBifidobacterium in the intestinal microbiome and SNPs in the hypolactasia associated LCT locus of the human genome, but also found evidence of interaction between host genetics and diet in regulating microbiome composition.
13. Blekhman, R., Goodrich, J.K., Huang, K., Sun, Q., Bukowski, R., Bell, J.T., Spector, T.D., Keinan, A., Ley, R.E., Gevers, D., et al. Host genetic variation impacts microbiome composition across human body sites. Genome Biol, 16, 2015, 191.
14. Sanders, M.E., Benson, A., Lebeer, S., Merenstein, D.J., Klaenhammer, T.R., Shared mechanisms among probiotic taxa: implications for general probiotic claims. Curr Opin Biotechnol 49 (2018), 207–216.
15. Hempel, S., Newberry, S.J., Maher, A.R., Wang, Z., Miles, J.N., Shanman, R., Johnsen, B., Shekelle, P.G., Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307 (2012), 1959–1969.
16. Lau, C.S., Chamberlain, R.S., Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Int J Gen Med 9 (2016), 27–37.
17. Aceti, A., Gori, D., Barone, G., Callegari, M.L., Di Mauro, A., Fantini, M.P., Indrio, F., Maggio, L., Meneghin, F., Morelli, L., et al. Probiotics for prevention of necrotizing enterocolitis in preterm infants: systematic review and meta-analysis. Ital J Pediatr, 41, 2015, 89.
18. Lee, I.C., Tomita, S., Kleerebezem, M., Bron, P.A., The quest for probiotic effector molecules–unraveling strain specificity at the molecular level. Pharmacol Res 69 (2013), 61–74.
19. Corr, S.C., Li, Y., Riedel, C.U., O'Toole, P.W., Hill, C., Gahan, C.G., Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci U S A 104 (2007), 7617–7621.
20. Yan, F., Polk, D.B., Characterization of a probiotic-derived soluble protein which reveals a mechanism of preventive and treatment effects of probiotics on intestinal inflammatory diseases. Gut Microbes 3 (2012), 25–28.
21. Fernandez-Gutierrez, M.M., Roosjen, P.P.J., Ultee, E., Agelink, M., Vervoort, J.J.M., Keijser, B., Wells, J.M., Kleerebezem, M., Streptococcus salivarius MS-oral-D6 promotes gingival re-epithelialization in vitro through a secreted serine protease. Sci Rep, 7, 2017, 11100.
22. Mohammedsaeed, W., Cruickshank, S., McBain, A.J., O'Neill, C.A., Lactobacillus rhamnosus GG lysate increases re-epithelialization of keratinocyte scratch assays by promoting migration. Sci Rep, 5, 2015, 16147.
23. van Baarlen, P., Troost, F., van der Meer, C., Hooiveld, G., Boekschoten, M., Brummer, R.J., Kleerebezem, M., Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc Natl Acad Sci U S A 108:Suppl. 1 (2011), 4562–4569.
24. Bron, P.A., van Baarlen, P., Kleerebezem, M., Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa. Nat Rev Microbiol 10 (2011), 66–78.
25. Zeilstra, D., Younes, J.A., Brummer, R.J., Kleerebezem, M., Fundamental limitations of the RCT method in nutritional research: the example of probiotics. Adv Nutr 9 (2018), 561–571, 10.1093/advances/nmy046 This study systematically analyzes the presuppositions that are intrinsic to the Randomized Controlled Trial (RCT) design and provides arguments why such clinical trial design may therefore be unsuitable for proving the efficacy of probiotics, as well as other nutritional inteventions.
26. Hardy, A., Benford, D., Halldorsson, T., Jeger, M.J., Knutsen, H.K., More, S., Naegeli, H., Noteborn, H., Ockleford, C., Ricci, A., et al. Guidance on the assessment of the biological relevance of data in scientific assessments. EFSA J, 15, 2017.
27. Larcombe, S., Hutton, M.L., Lyras, D., Involvement of bacteria other than Clostridium difficile in antibiotic-associated diarrhoea. Trends Microbiol 24 (2016), 463–476.
28. Rineh, A., Kelso, M.J., Vatansever, F., Tegos, G.P., Hamblin, M.R., Clostridium difficile infection: molecular pathogenesis and novel therapeutics. Expert Rev Anti Infect Ther 12 (2014), 131–150.
29. Dadar, M., Tiwari, R., Karthik, K., Chakraborty, S., Shahali, Y., Dhama, K., Candida albicans - biology, molecular characterization, pathogenicity, and advances in diagnosis and control - an update. Microb Pathog 117 (2018), 128–138.
30. Delcaru, C., Alexandru, I., Podgoreanu, P., Cristea, V.C., Bleotu, C., Chifiriuc, M.C., Bezirtzoglou, E., Lazar, V., Antagonistic activities of some Bifidobacterium sp. strains isolated from resident infant gastrointestinal microbiota on gram-negative enteric pathogens. Anaerobe 39 (2016), 39–44.
31. Schoster, A., Kokotovic, B., Permin, A., Pedersen, P.D., Dal Bello, F., Guardabassi, L., In vitro inhibition of Clostridium difficile and Clostridium perfringens by commercial probiotic strains. Anaerobe 20 (2013), 36–41.
32. Mills, S., Ross, R.P., Hill, C., Bacteriocins and bacteriophage; a narrow-minded approach to food and gut microbiology. FEMS Microbiol Rev 41 (2017), S129–S153.
33. Surendran Nair, M., Amalaradjou, M.A., Venkitanarayanan, K., Antivirulence properties of probiotics in combating microbial pathogenesis. Adv Appl Microbiol 98 (2017), 1–29.
34. Engelbrektson, A., Korzenik, J.R., Pittler, A., Sanders, M.E., Klaenhammer, T.R., Leyer, G., Kitts, C.L., Probiotics to minimize the disruption of faecal microbiota in healthy subjects undergoing antibiotic therapy. J Med Microbiol 58 (2009), 663–670 This study describes the possibility of the improved resilience of the gut microbiome to recover after antibiotic treatment, a concept of probiotic functionality that is important to consider in this context.
35. Moens, F., Verce, M., De Vuyst, L., Lactate- and acetate-based cross-feeding interactions between selected strains of lactobacilli, bifidobacteria and colon bacteria in the presence of inulin-type fructans. Int J Food Microbiol 241 (2017), 225–236.
36. Bron, P.A., Kleerebezem, M., Brummer, R.J., Cani, P.D., Mercenier, A., MacDonald, T.T., Garcia-Rodenas, C.L., Wells, J.M., Can probiotics modulate human disease by impacting intestinal barrier function?. Br J Nutr 117 (2017), 93–107.
37. Fukuda, S., Toh, H., Hase, K., Oshima, K., Nakanishi, Y., Yoshimura, K., Tobe, T., Clarke, J.M., Topping, D.L., Suzuki, T., et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469 (2011), 543–547.
38. Neu, J., Walker, W.A., Necrotizing enterocolitis. N Engl J Med 364 (2011), 255–264.
39. Elgin, T.G., Kern, S.L., McElroy, S.J., Development of the neonatal intestinal microbiome and its association with necrotizing enterocolitis. Clin Ther 38 (2016), 706–715.
40. Underwood, M.A., Impact of probiotics on necrotizing enterocolitis. Semin Perinatol 41 (2017), 41–51.
41. Underwood, M.A., Davis, J.C.C., Kalanetra, K.M., Gehlot, S., Patole, S., Tancredi, D.J., Mills, D.A., Lebrilla, C.B., Simmer, K., Digestion of human milk oligosaccharides by Bifidobacterium breve in the premature infant. J Pediatr Gastroenterol Nutr 65 (2017), 449–455.
42. Garrido, D., Ruiz-Moyano, S., Kirmiz, N., Davis, J.C., Totten, S.M., Lemay, D.G., Ugalde, J.A., German, J.B., Lebrilla, C.B., Mills, D.A., A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596. Sci Rep, 6, 2016, 35045.
43. Frese, S.A., Hutton, A.A., Contreras, L.N., Shaw, C.A., Palumbo, M.C., Casaburi, G., Xu, G., Davis, J.C.C., Lebrilla, C.B., Henrick, B.M., et al. Persistence of supplemented Bifidobacterium longum subsp. infantis EVC001 in breastfed infants. mSphere, 2, 2017.
44. Afrazi, A., Branca, M.F., Sodhi, C.P., Good, M., Yamaguchi, Y., Egan, C.E., Lu, P., Jia, H., Shaffiey, S., Lin, J., et al. Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis. J Biol Chem 289 (2014), 9584–9599.
45. Patel, R.M., Denning, P.W., Therapeutic use of prebiotics, probiotics, and postbiotics to prevent necrotizing enterocolitis: what is the current evidence?. Clin Perinatol 40 (2013), 11–25.
46. Patel, R.M., Denning, P.W., Intestinal microbiota and its relationship with necrotizing enterocolitis. Pediatr Res 78 (2015), 232–238.
47. Ganguli, K., Collado, M.C., Rautava, J., Lu, L., Satokari, R., von Ossowski, I., Reunanen, J., de Vos, W.M., Palva, A., Isolauri, E., et al. Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut. Pediatr Res 77 (2015), 528–535.
48. Meng, D., Zhu, W., Ganguli, K., Shi, H.N., Walker, W.A., Anti-inflammatory effects of Bifidobacterium longum subsp infantis secretions on fetal human enterocytes are mediated by TLR-4 receptors. Am J Physiol Gastrointest Liver Physiol 311 (2016), G744–G753 This study demonstrated that probably a glycan or acyl-glycan in the conditioned media ofBifidobacterium longum subspecies infantis is able to modulate TLR-4 dependent signalling in human cells and could thereby play a critical role in the protective effect of this probiotic in NEC, since TLR-4 is considered to play a significant role in induction of NEC.