PREBIOTICI E MICROBIOMA:QUALE CONTRIBUTO NELLA PRATICA

CLINICA

MANZO TERESAPEDIATRA DI FAMIGLIA ASL NA3 SUD

World Gastroenterology Organization Global Guidelines Probiotics and prebiotics October 2011

NATURA CHIMICA DEI PREBIOTICI

Commonly known prebiotics are: • Oligofructose(FOS) • Inulin • Galacto-oligosaccharides (GOS) • Lactulose • Breast milk oligosaccharides World Gastroenterology Organisation Global Guidelines Probiotics and prebiotics October 2011

MECCANISMO D’AZIONE

Prebiotics affect intestinal bacteria by increasing the numbers of beneficial anaerobic bacteria(e.g.bifidobacterium and lactobacillus) and decreasing the population of potentially pathogenic microorganisms

World Gastroenterology Organisation Global Guidelines Probiotics and prebiotics October 2011

MICROBIOMA UMANO

•The collective genomes of our microbial symbionts

• «The Human Microbiome Projectt». Nature 449: 804-810 (18 October 2007)

DEFINIZIONE DI MICROBIOTA

• INSIEME DEI MICRORGANISMI CHE COLONIZZANO IL CORPO UMANO

• ESSI RISIEDONO SULLA PELLE,NEL TRATTO RESPIRATORIO,NEL TRATTO VAGINALE E SOPRATTUTTO NELL’APPARATO GASTRO-ENTERICO(IN PARTICOLARE COLON)

Intestinal Microbiota

• Includes bacteria, archea (single-celled prokaryotes), viruses, fungi and parasites

• > 50 bacterial phyla described– Majority anaerobic– Constitute 60% of dry weight

of feces– Bacteroides, Firmicutes,

Actinobacteria, Proteobacteria– 1014 bacterial cells 10 times

greater than number of human cells in our body

Eckburg, PB et al. Science 2005:308;1635-8

Pediatrics 2012;129:950–960

The pool of microbes inhabiting our body is known as “microbiota” and their collective genomes as “microbiome”. The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life.World J Gastroenterol. 2014 Nov 7; 20(41): 15163–15176.

Disease states that have been associated with altered GI microbiota (adapted from Sanders, 2011)

Atopy (allergy) and asthma

Coeliac disease

Colon cancer

Type I diabetes

Type II diabetes

HIV infection

Inflammatory bowel disease (IBD)

Irritable bowel syndrome (IBS)

GI infections

Antibiotic-associated diarrhoea (AAD)

Necrotising enterocolitis

Obesity

Rheumatoid arthritis

I PREBIOTICI POSSONO ACCELERARE O MIGLIORARE LA CORREZIONE DEL

MICROBIOTA IN SEGUITO AD UN INSULTO?

The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. World J Gastroenterol. 2014 Nov 7; 20(41): 15163–15176

Gut 2013;62:159–176

Currently Available Strategies for Modifying Gut Microbiota

Br J Nutr. 2014 Dec 28;112(12):2068-74. doi: 10.1017/S0007114514003110. Epub 2014 Oct 20.Effect of oligofructose supplementation on body weight in overweight and obese children: a randomised, double-blind, placebo-controlled trial.Liber A1, Szajewska H1.

Conclusions: oligofructose supplementation for 12 weeks has no effect on body weight in overweight and obese children.

J Pediatr. 2013 Nov;163(5):1272-7.e1-2. doi: 10.1016/j.jpeds.2013.05.035.

Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial.

Pärtty A1, Luoto R, Kalliomäki M, Salminen S, Isolauri ECONCLUSIONS: Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants. This original finding may offer new therapeutic and preventive measures for this common disturbance in early life

J Am Coll Nutr. 2014;33(5):385-93. doi: 10.1080/07315724.2013.878232. Epub 2014 Oct 10.Prebiotic effect of an infant formula supplemented with galacto-oligosaccharides: randomized multicenter trial.Giovannini M1, Verduci E, Gregori D, Ballali S, Soldi S, Ghisleni D, Riva ECONCLUSIONS: The prebiotic-supplemented formula mimicked the effect of human milk in promoting Bifidobacterium and Lactobacillus growth and in inhibiting Clostridium growth, resulting in a significantly lower presence of colic

Nutr J. 2014 Jul 24;13:75. doi: 10.1186/1475-2891-13-75.Effect of yogurt containing polydextrose, Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019: a randomized, double-blind, controlled study in chronic constipation.Magro DO1, de Oliveira LM, Bernasconi I, Ruela Mde S, Credidio L, Barcelos IK, Leal RF, Ayrizono Mde L, Fagundes JJ, Teixeira Lde B, Ouwehand AC, Coy CS.Author informationCONCLUSION: The product containing yogurt with polydextrose, B. lactis HN019 and L. acidophilus NCFM® significantly shortened colonic transit time after two weeks in the TG compared to CG and may be an option for treatment of constipation

Pediatrics. 2014 Jun;133(6):e1533-40. doi: 10.1542/peds.2013-3598.Follow-up formula(FUF) (containing DHA,prebiotics PDX and GOS) consumption in 3- to 4-year-olds and respiratory infections: an RCT.Li F1, Jin X1, Liu B2, Zhuang W2, Scalabrin D3

CONCLUSIONS: Daily consumption of a FUF containing DHA, the prebiotics PDX and GOS, and yeast β-glucan was associated with fewer episodes and shorter duration of ARI, as well as less antibiotic use. The children who consumed the FUF had increased interleukin-10 and white blood cells, suggesting an antiinflammatory mechanism and/or an increase of effector immune cells

J Pediatr Gastroenterol Nutr. 2014 Apr;58(4):428-37. doi: 10.1097/MPG.0000000000000252.Effects of growing-up milk supplemented with prebiotics and LCPUFAs on infections in young children.Chatchatee P1, Lee WS, Carrilho E, Kosuwon P, Simakachorn N, Yavuz Y, Schouten B, Graaff PL, Szajewska HCONCLUSIONS: This is the first study in children to show a reduced risk of infection following consumption of GUM supplemented with scGOS/lcFOS/n-3 LCPUFAs. The borderline statistical significance justifies a new study to confirm this finding

Br J Nutr. 2011 Dec;106(11):1740-8. doi: 10.1017/S0007114511004053. Epub 2011 Oct 4.Do prebiotics reduce the number of fever episodes in healthy children in their first year of life: a randomised controlled trial.van Stuijvenberg M1, Eisses AM, Grüber C, Mosca F, Arslanoglu S, Chirico G, Braegger CP, Riedler J, Boehm G, Sauer PJCONCLUSION: There was no effect of adding specific prebiotics to standard formula feeding in reducing the number of fever episodes in the present study.

Int Med Res. 2013 Oct;41(5):1426-36. doi: 10.1177/0300060513493692. Epub 2013 Aug 1.Meta-analysis of probiotics and/or prebiotics for the prevention of eczema.Dang D1, Zhou W, Lun ZJ, Mu X, Wang DX, Wu H.CONCLUSION: This meta-analysis found that probiotics or synbiotics may reduce the incidence of eczema in infants aged <2 years. Systemic sensitization did not change following probiotic administration

Immunotherapy. 2013 Aug;5(8):869-78. doi: 10.2217/imt.13.85.Understanding the role of probiotics and prebiotics in preventing allergic disease: evidence and methodological issues.Szajewska H1.AbstractThis paper briefly summarizes evidence regarding the role of probiotics and/or prebiotics in reducing the risk of allergy. There are studies that show a protective effect, no effect or even a predisposing effect of using probiotics and/or prebiotics in preventing allergic disease. A variety of methodological issues are likely to contribute to current uncertainty. These include differences in the study population (high-risk vs unselected population), optimal strain selection (all probiotics are not equal), differences in definitions of outcomes, timing and duration of the interventions, and a lack of repeat studies

Cancer Lett. 2014 Apr 10;345(2):258-70. doi: 10.1016/j.canlet.2013.08.013. Epub 2013 Aug 24.Gastrointestinal cancers: influence of gut microbiota, probiotics and prebioticsConclusions: More research is required to reveal the interactions of microflora with genetic, epigenetic and immunologic factors, diet and age, before any firm conclusion be drawn. Well-designed, randomized, double blind, placebo-controlled human studies using probiotics and/or prebiotics, with adequate follow-up are necessary in order to formulate directions for prevention and therapy

Br J Nutr. 2013 Oct;110(7):1292-303. doi: 10.1017/S000711451300055X. Epub 2013 Mar 14.

Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial.

Whisner CM1, Martin BR, Schoterman MH, Nakatsu CH, McCabe LD, McCabe GP, Wastney ME, van den Heuvel EG, Weaver CMThe results suggest that daily consumption of 5 g GOS increases Ca absorption, which may be mediated by the gut microbiota, specifically bifidobacteria

BMC Pediatr. 2012 Aug 7;12:118. doi: 10.1186/1471-2431-12-118.

Total calcium absorption is similar from infant formulas with and without prebiotics and exceeds that in human milk-fed infants.

Hicks PD1, Hawthorne KM, Berseth CL, Marunycz JD, Heubi JE, Abrams

No significant effect of prebiotics was observed on calcium absorption or other markers of bone mineral metabolism.

J Food Microbiol. 2007 Apr 1;115(1):1-11. Inflammatory bowel disease: current insights into pathogenesis and new therapeutic options; probiotics, prebiotics and synbiotics.Geier MS1, Butler RN, Howarth GSPrebiotics have been studied less extensively, however, they may become an ideal treatment or co-treatment option due to their capacity to increase endogenous lactobacillus and bifidobacteria. Probiotics and prebiotics may offer a new therapeutic option for the treatment of IBD, however, a greater understanding of the mechanisms behind their action on the gastrointestinal microbiota is required in order to determine which probiotic, prebiotic or combinations thereof are the most beneficial.

The American Journal of Gastroenterology 109, 1547-1561 (October 2014) Efficacy of Prebiotics, Probiotics, and Synbiotics in Irritable Bowel Syndrome and Chronic Idiopathic Constipation: Systematic Review and Meta-analysis

CONCLUSIONS:Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC(chronic idiopathic constipation) is also uncertain

Am J Gastroenterol. 2014 Oct;109(10):1563-5. Editorial: The importance of systematic reviews and meta-analyses of probiotics and prebiotics.Whelan K1.AbstractA systematic review and meta-analysis of the evidence for probiotics, prebiotics, and synbiotics in IBS and chronic idiopathic constipation has recently been performed. By far, the most convincing evidence was for the use of probiotics in IBS,…..However, only a minority of the trials were at a low risk of bias, and some used small sample sizes. Meta-analysis is a powerful tool to combine individual small trials to improve the power to detect the direction, size, and consistency of an effect, but it can do little to overcome the poor design of individual trials.

Future Microbiol. 2015;10(5):889-902. doi: 10.2217/fmb.15.13.Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease(NAFLD)Tarantino G1, Finelli CCONCLUSION:Although probiotics and prebiotics have been proposed in the treatment and prevention of patients with obesity-related NAFLD, their therapeutic use is not supported by high-quality clinical studies.

Many debate the use of meta-analysis to combine data from different probiotic species, strains, or combinations. It is recommended that all future meta-analyses of probiotics, in any clinical setting, perform subgroup analysis on specific species/strains and specific combinations..

KEY MESSAGE:ULTERIORI PROVE DI CONFERMA SONO NECESSARIEPRIMA DI UNA RACCOMANDAZIONE PER L’USO DI ROUTINE DEI PREBIOTICI