Human Gut Mycobiota is still a mistery for us. Most of the reasearch on this topichas been conducted in the last 5 years. We are starting to comprehend the interactions with our gastrointestinal system and the virus and bacterial communities. 13% of gut microbiota in weight, about 150 species; most of them can shift from commensalism to virulent parassitosis according to our immune competence. Gut fungal overgrowth is actually underestimated in dignaosis and treatment. Many FGIDS and SIBO are frequently mixed bacteral and fungal dysbiosis
2. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
3. Pubmed search for Mycobiota 24 Settembre 2018
370 results
Filter «Humans» «In the last 5 Years
49 results
16 Reviews
4. PROBIOTICI
Bacterial Yeast
Prokaryotic (DNA loose in cytoplasm) Eukaryotic (nucleus)
Small Large size
AB-resistant genes + transfer between ≠ spp No antibiotic-resistant genes
Affected by AB Not affected by AB
Resistant to proteolysis
S. boulardii: more persistent, optimum growth at
37°C, resistant to low pH (survival gastric acidiy),
tolerant to bile salts
Dth: 1-2 x 1010 /day concstool: 2 x 108 / g stool
Steady state: three days Telim: 3-5 days
Elmer et al. found that some types of fiber
(psyllium) increased SB levels by 22 %
5. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
6. Figure 1. The archaeal and fungal components of the human gut microbiome.
Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, et al. (2013) Archaea and Fungi of the Human Gut Microbiome: Correlations with
Diet and Bacterial Residents. PLOS ONE 8(6): e66019. https://doi.org/10.1371/journal.pone.0066019
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066019
UPDATE CLASSIFICATION
Mycobank
http://www.mycobank.org/
Index Fungorum
http://www.indexfungorum.org/
names/names.asp
7. Figure 2. Analysis of co-occurrence among microbial lineages scored using the Dice index.
Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, et al. (2013) Archaea and Fungi of the Human Gut Microbiome: Correlations with
Diet and Bacterial Residents. PLOS ONE 8(6): e66019. https://doi.org/10.1371/journal.pone.0066019
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066019
8. Nat Rev Immunol. 2017 Oct;17(10):635-646.
«1 miliardo di anni fa
funghi e animali si sono
staccati dal ramo evolutivo
delle piante trovando nelle
nuove vie evolutive molti
modi di interazione
mutualmente reciproca»
9. Figure 3. Inter-generic relationships.
Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, et al. (2013) Archaea and Fungi of the Human Gut Microbiome: Correlations with
Diet and Bacterial Residents. PLOS ONE 8(6): e66019. https://doi.org/10.1371/journal.pone.0066019
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066019
10. Gut Mycobiota
13% of total microbiota
(wheight)
140 genus
mainly Basidiomycota
and Ascomycota
- Schei et al. Microbiome (2017) 5:107
- Hamad et al. Repertory of eukaryotes (eukaryome) in the human gastrointestinal
tract: taxonomy and detection methods. Parasite Immunol. 2016;38:12–36
11. Gut Mycobiota
RESIDENTI IN TRANSITO
- Temperature 37°
- Low oxigen atmosphere
- Wide pH variations
- Biliar salts
- Gastric acid
- Digestive enzimes
12. FEMS Microbiol Rev. 2017 Jul 1;41(4):479-511. doi: 10.1093/femsre/fuw047.
Forgotten fungi-the gut mycobiome in
human health and disease.
13. Gut Mycobiota
Hamad et al.
Repertory of
eukaryotes
(eukaryome) in the
human
gastrointestinal
tract: taxonomy
and detection
methods. Parasite
Immunol.
2016;38:12–36
14. FEMS Microbiol Rev. 2017 Jul 1;41(4):479-511. doi: 10.1093/femsre/fuw047.
Forgotten fungi-the gut mycobiome in
human health and disease.
16. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
17. Int. J. Mol. Sci. 2017, 18, 330;
doi:10.3390/ijms18020330
18. Figure 6. Possible syntrophic relationships in the human gut consistent with data reported in this
study.
Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, et al. (2013) Archaea and Fungi of the Human Gut Microbiome: Correlations with
Diet and Bacterial Residents. PLOS ONE 8(6): e66019. https://doi.org/10.1371/journal.pone.0066019
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066019
26. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
27. Timeline of studies published on the gut
mycobiome and colour coded as follows: major
developments (grey), GI disease (blue),
immunocompromised hosts (red), healthy
populations (yellow), infants (purple), diet
(green) and other (teal).
FEMS Microbiol Rev. 2017 Jul 1;41(4):479-511. doi: 10.1093/femsre/fuw047.
Forgotten fungi-the gut mycobiome in
human health and disease.
28.
29. - 26 % (24/94) and 25.3 % (38/150) of a series of
patients with unexplained GI symptoms had SIFO
- symptoms observed in these patients were belching,
bloating, indigestion, nausea, diarrhea, and gas
- small intestinal dysmotility and use of proton pump
inhibitors are possible underlying mechanism(s)
- a 2–3-week course of antifungal therapy is
recommended and may be effective in improving
symptoms, but evidence for eradication is lacking
33. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
34. Mycobiota and th Human Exposome
The chemical spectra of molecules in the organism is believed to
account for :
- about 40 nutrients
- 2,000 intermediary metabolites
- 200,000 peptides
- 500.000 lipids
- 400,000 sostanze chimiche
- Circa 300 micotossine principalmente da Fusarium, Claviceps,
Alternaria, Aspergillus, Candida e Penicillium (Marin et al., 2013).
Molte di queste sono di origine batterica o fungina…
40. Disease Markers Volume 2018, Article ID 7451946, 16 pages
https://doi.org/10.1155/2018/7451946
ASCA, I2, and
OmpC altogether
can be found in
80% of patients
with CD
41. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
42.
43. Nature reviews Fungal Dysbiosis – 2017
Iliev, I. D., & Leonardi, I. (2017). Fungal dysbiosis: immunity and
interactions at mucosal barriers. Nature Reviews Immunology,
17(10), 635–646. doi:10.1038/nri.2017.55
47. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
49. Zuo, T., Kamm, M. A., Colombel, J.-F., & Ng, S. C. (2018).
Urbanization and the gut microbiota in
health and inflammatory bowel disease.
Nature Reviews Gastroenterology &
Hepatology, 15(7), 440–452.
doi:10.1038/s41575-018-0003-z
50. Zuo, T., Kamm, M. A., Colombel, J.-F., & Ng, S. C. (2018). Urbanization and the gut microbiota in health
and inflammatory bowel disease. Nature Reviews Gastroenterology & Hepatology,
15(7), 440–452. doi:10.1038/s41575-018-0003-z
51. Zuo, T., Kamm, M. A., Colombel, J.-F., & Ng, S. C. (2018). Urbanization and the gut microbiota in health
and inflammatory bowel disease. Nature Reviews Gastroenterology & Hepatology,
15(7), 440–452. doi:10.1038/s41575-018-0003-z
52. High-Fat Diet Changes Fungal Microbiomes and Interkingdom
Relationships in the Murine Gut
mSphere 2017 Oct 11;2(5). pii: e00351-17. doi: 10.1128/mSphere.00351-17.
eCollection 2017 Sep-Oct.
55. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
56.
57.
58. the Basidiomycota:Ascomycota ratio and the
Candida albicans count were found to be
increased, while Saccharomyces cerevisiae
abundance decreased.
Other species’ numbers found elevated in CD
included Gibberella moniliformis,
Alternaria brassicicola and Cryptococcus
neoformans.
It is of interest that fungal microbiota correlated
with the CD activity index and the degree of
inflammation expressed by C-reactive protein
(CRP) concentration.
59.
60. Mycobiota e Dieta
Hallen-Adams HE, Kachman SD, Kim J, Legge RM, Martınez I. Fungi inhabiting the healthy human gastrointestinal tract: a diverse and
dynamic community. Fungal Ecol 2015; 15:9-17; http://dx.doi.org/10.1016/j.funeco. 2015.01.006
Suhr MJ, Banjara N, Hallen-Adams HE. Sequence-based methods for detecting and evaluating the human gut mycobiome. Lett Appl Microbiol
2016; 62:209-15; PMID:26669281; http://dx.doi.org/10.1111/lam.12539
_________
61. Figure 5. Fungi-Diet relationships.
Hoffmann C, Dollive S, Grunberg S, Chen J, Li H, et al. (2013) Archaea and Fungi of the Human Gut Microbiome: Correlations with Diet and
Bacterial Residents. PLOS ONE 8(6): e66019. https://doi.org/10.1371/journal.pone.0066019
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066019
62. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
63. McFarland LV, (2010). Systematic review and meta-analysis of Saccharomyces boulardii in adult
patients,
world J Gastroenterol, 16 (18), 2202-2222.
Probiotics: live microorganisms that confer a health benefit on the host
Saccharomyces boulardii (S.B.)
•SB was found to be sign. efficacious and safe in 84% of all treatment arms (26/31), 27 ≠trials.
•SB sign. effective in preventing antibiotic-associated diarrhea (AAD (p <0.001)
•In adults, recommended for prevention of AAD and traveler’s diarrhea
•Prevention of enteral nutrition related diarrhea and reduction of Heliobacter pylori treatment-
related symptoms
•Promise for prevention of C. difficile disease recurrences, irritable bowel syndrome, acute adult
diarrhea, Chron’s disease, giardiasis, human immunodeficiency virus-related diarrhea
McFarland LV, (2010). Systematic review and meta-analysis of Saccharomyces boulardii in adult patients, world J Gastroenterol, 16 (18), 2202-2222
64. Potentially, probiotics maintain or restore gut microecology during or after
antibiotic treatment through:
- receptor competition,
- competition for nutrients,
- inhibition of epithelial and mucosal adherence of pathogens,
- introduction of lower colonic pH favoring the growth of nonpathogenic species,
- stimulation of immunity, or production of antimicrobial substances.4,5
71. Szajewska_2009
Szajewska H, Skórka A. Saccharomyces boulardii for treating acute
gastroenteritis in children: updated meta-analysis of randomized
controlled trials. Alimentary Pharmacology & Therapeutics 2009;30:
960–1.
In conclusion, this update of our meta-analysis of data from RCTs
confirms that in otherwise healthy infants and children, the use of
S. boulardii is associated with clinical benefits in the treatment of
AGE, specifically a reduction in the duration of diarrhoea by
approximately 1 day.
Saccharomyces boulardii: Meta-analysis using data from 7 RCTs: 944
healthy children with acute gastroenteritis.
The duration of diarrhea was reduced with 1.08 days (95% CI: 0.53-
1.64) in children who received the yeast compared with placebo.
72. Szajewska_2001: http://www.ncbi.nlm.nih.gov/pubmed/11698781
Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhoea in infants and
children; a systematic review of published randomized, double-blind, placebo-controlled trials. Journal of
Pediatric Gastroenterology and Nutrition 2001;33 Suppl 2:17–25.
BACKGROUND: This review was designed to assess the evidence from randomized controlled trials on effects of
probiotics in the treatment and prevention of acute infectious diarrhea in infants and children.
METHODS: A systematic review of published, randomized, double-blind, placebo-controlled trials on probiotics in the
treatment or prevention of acute diarrhea defined as >3 loose or watery stools per 24 hours in infants and
children.
RESULTS: The use of probiotics as compared with placebo was associated with a significantly reduced risk of diarrhea
lasting >3 days. The pooled estimate risk was 0.43 (95% CI, 0.34-0.53) with a fixed-effect model, and remained
significant in a random-effect model (0.40; 95% CI, 0.28-0.57). Only Lactobacillus GG showed a consistent effect.
Probiotics significantly reduced the duration of diarrhea when compared with placebo, particularly in rotaviral
gastroenteritis-the pooled, weighted, mean difference (WMD) assuming the random-effect model was -20.1 hours
(95% CI, -26.1 to -14.2) and -24.8 (95% CI, -31.8 to -17.9) respectively. A meta-analysis of the prevention studies
was not feasible because of significant clinical and statistical heterogeneity.
CONCLUSIONS: There is evidence of a clinically significant benefit of probiotics in the treatment of acute infectious
diarrhea in infants and children, particularly in rotaviral gastroenteritis. Lactobacillus GG showed the most
consistent effect, although other probiotic strains may also be effective. Further research is needed. Clinical and
statistical heterogeneity of the prophylactic interventions preclude drawing firm conclusions about the efficacy of
probiotics in preventing acute gastroenteritis.
The risk of diarrhea lasting three or more days was reduced by 0.40 in the probiotic compared with the placebo group
(8 studies included; 731 children), and probiotics reduced the duration of diarrhea by 18.2 hours (n=8, 773
children).
73. Van Niel_2002: http://pediatrics.aappublications.org/content/109/4/678
Van Niel CW, Feudtner C, Garrison MM, Christakis DA. Lactobacillus therapy for acute infectious diarrhoea in children: a
meta-analysis. Pediatrics 2002;109(4):678–84.
Objective. Childhood diarrhea accounts for substantial morbidity and mortality worldwide. Multiple studies in children
have shown that Lactobacillus, administered orally, may have antidiarrheal properties. We conducted a meta-
analysis of randomized, controlled studies to assess whether treatment with Lactobacillus improves clinical
outcomes in children with acute infectious diarrhea.
Methods. Studies were sought in bibliographic databases of traditional biomedical as well as complementary and
alternative medicine literature published from 1966 to 2000. Search terms were “competitive inhibition,”
“diarrhea,” “gastroenteritis,” “Lactobacillus,” “probiotic,” “rotavirus,” and “yog(h)urt.” We included studies that
were adequately randomized, blinded, controlled trials in which the treatment group received Lactobacillus and
the control group received an adequate placebo and that reported clinical outcome measures of diarrhea
intensity. These inclusion criteria were applied by blind review and consensus. The original search yielded 26
studies, 9 of which met the criteria. Multiple observers independently extracted study characteristics and clinical
outcomes. Data sufficient to perform meta-analysis of the effect of Lactobacillus on diarrhea duration and
diarrhea frequency on day 2 were contained in 7 and 3 of the included studies, respectively.
Results. Summary point estimates indicate a reduction in diarrhea duration of 0.7 days (95% confidence interval: 0.3–
1.2 days) and a reduction in diarrhea frequency of 1.6 stools on day 2 of treatment (95% confidence interval: 0.7–
2.6 fewer stools) in the participants who received Lactobacillus compared with those who received placebo.
Details of treatment protocols varied among the studies. A preplanned subanalysis suggests a dose-effect
relationship.
Conclusion. The results of this meta-analysis suggest that Lactobacillus is safe and effective as a treatment for children
with acute infectious diarrhea.
Different lactobacilli strains. Probiotics reduced the duration of diarrhea with 0.7 days, and diarrhea frequency on day 2
by 1.6 (3 studies, 122 children).
74. Szajewska_2007a
Szajewska 2007b Szajewska H, Skórka A, Dylag M. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea
in children. Alimentary Pharmacology & Therapeutics 2007;25: 257–64.
AIM: To review evidence for the effectiveness of Lactobacillus casei GG (LGG) in treating acute infectious diarrhoea in
children.
METHODS: The following electronic databases were searched through August 2006 for studies relevant to acute
infectious diarrhoea and LGG: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were
obtained from reviewed articles. Only randomized-controlled trials (RCTs) were included.
RESULTS: Eight RCTs (988 participants) met the inclusion criteria. Compared with controls, LGG had no effect on the
total stool volume (two RCTs, n = 303). However, LGG was associated with a significant reduction in diarrhoea
duration (seven RCTs, 876 infants, weighted mean difference, WMD -1.1 days (95% confidence interval, CI -1.9 to -
0.3), particularly of rotavirus etiology (WMD -2.1 days, 95% CI -3.6 to -0.6), risk of diarrhoea >7 days (one RCT, n =
287, relative risk 0.25, 95% CI 0.09-0.75) and duration of hospitalization (three RCTs, n = 535, WMD -0.58, 95% CI -
0.8 to -0.4; significance was lost in the random effect model). There was no reduction in the number of stools at
any time interval.
CONCLUSIONS: The use of LGG is associated with moderate clinical benefits in the treatment of acute diarrhoea in
children. These findings should be interpreted with caution due to the important methodological limitations and
heterogeneity of most of the studies.
Studies involving Lactobacillus casei GG, L casei GG reduced the duration of diarrhea by 1.1 days (7 trials, 876 infants)
and was particularly effective in rotavirus diarrhea (duration reduced by 2.1 days).
75. Chmielewska 2008
Chmielewska A, RuszczyńskiM, Szajewska H. Lactobacillus reuteri strain ATCC 55730 for the treatment of acute
infectious diarrhea in children: a meta-analysis of randomized controlled trials. Metaanalysis 2008;10:32–6.
Background Probiotics may be of help for the management of acute diarrhoea, however, the effect is strain specific and
efficacy needs to be proven.
Aim To test the efficacy and safety of Lactobacillus reuteri DSM 17938 derived from L. reuteri ATCC 55730 in
children with acute diarrhoea. Primary outcomes were the rate of unresolved diarrhoea after 3 days of treatment
and duration of diarrhoea.
Methods Children (6–36 months), hospitalised in three paediatric hospitals in Southern Italy for acute diarrhoea
with clinical signs of dehydration were randomised to receive in a double-blind fashion either L. reuteri (dose of 4
× 108 colony-forming units/die) or placebo.
Results Out of 96 eligible children, 74 were enrolled, five patients were withdrawn; 35 in the L. reuteri group and
34 in the placebo group. Lactobacillus reuteri significantly reduced the duration of watery diarrhoea as compared
with placebo (2.1 ± 1.7 days vs. 3.3 ± 2.1 days; P < 0.03); on day two and three of treatment watery diarrhoea
persisted in 82% and 74% of the placebo and 55% and 45% of the L. reuteri recipients respectively (P < 0.01; P <
0.03). Finally, children receiving L. reuteri had a significantly lower relapse rate of diarrhoea (15% vs. 42%; P <
0.03). There was not a significant difference in hospital stay between the groups. No adverse events were
recorded.
Conclusion Our study shows that L. reuteri DSM 17938 as an adjunct to rehydration therapy is efficacious in the
treatment of acute diarrhoea reducing the frequency, duration and recrudescence rate of the disease.
Meta-analysis of 2 studies using Lactobacillus reuteri DSM 17938. This probiotic reduced the duration of diarrhea by 22
hours.
76. Wolvers_2010
Wolvers D, Antoine JM, Myllyluoma E, Schrezenmeir J, Szajewska H, Rijkers GT. Guidance for
substantiating the evidence for beneficial effects of probiotics: prevention and management
of infections by probiotics. Journal of Nutrition 2010;140(3): 698S–712S.
Sufficient consistent data exist for the management of infectious diarrhea in infants and traveler's
diarrhea, antibiotic-associated diarrhea, and necrotizing enterocolitis to conclude that certain
probiotics, under certain conditions, and in certain target populations, are beneficial in
reducing the risk of infection.
Different Bacterial strains and Saccharomyces boulardii. The beneficial effects
of probiotics in acute infectious diearrhea were dependent on the strain of
bacteria and the dose (a greater effect with doses >1010-1011 colony
forming units (CFU/day)
77. McFarland L.V, Meta-Analysis of Probiotics for the Prevention of Antibiotic Associated
Diarrhea and the Treatment of Clostridium difficile Disease.
American Journal of Gastroenterology 2006, 101: 812-822.
Evidenze scientifiche
dell’efficacia di Saccharomyces boulardii
In caso di diarrea associata all’uso di antibiotici (DAA):
Diarrea acuta
78.
79. Disbiosi
- Clostridium Difficile Associated Diarrhea (CDAD**)
- riduzione delle difese immunitarie
- riduzione della sintesi di vitamine
- alterazione della funzione di barriera intestinale
(leaky gut)
Antibiotici
Riduzione della flora commensale
Oltre il 30% dei pazienti
Sviluppa una diarrea associata all’uso di antibiotici (DAA*)
Conseguenze:
Diarrea
- riduzione della qualità di vita
- doulori addominali
- gonfiore
- interruzione del trattamento con antibiotici
*AAD = Antibiotics Associated Diarrhea
*CDAD = Clostridium Difficile Associated Diarrhea
80. The use of antibiotics that disturb the gastrointestinal flora
is associated with clinical symptoms such as diarrhea,
which occurs in as many as 30% of patients.1,2 Symptoms
range from mild and self-limiting to severe, particularly in
Clostridium difficile infections, and antibiotic-associated
diarrhea (AAD) is an important reason for nonadherence
with antibiotic treatment.3
Probiotics for the Prevention and Treatment
of Antibiotic-Associated DiarrheaA Systematic
Review and Meta-analysis
JAMA. 2012;307(18):1959-1969. doi:10.1001/jama.2012.3507
81. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
88. Linee guida SIMAT per le
candidosi vulvo vaginali
Agente eziologico:
Candida albicans (80-92 %%), Candida glabrata,
Candida spp.
Feequenza:
Il 75% delle donne ha avuto almeno 1 episodio di
candidosi vaginale durante la propria vita. Il 40 - 45%
due o più episodi.
Sintomi:
prurito vulvare
dolore vulvare
secrezioni vaginali biancastre
dispareunia Superficiale
Segni:
eritema
secrezioni
lesioni satellite
edema
TRATTAMENTO FARMACOLOGICO
PER I CASI SINTOMATICI
(Il 20% delle donne ha colonizzazione ma non sintomi)
Opzioni terapeutiche
Fluconazolo CPR 150 mg, 1 CPR monosomm.
Itraconazolo cpr 200 mg, 1/die per 3 giorni.
Itraconazolo cpr 200 mg, 1 x 2/die per 1 giorno.
Clotrimazolo crema 1% applicazione intravaginale
(5 g) per 7 - 14 giorni.
Clotrimazolo candelette vaginali 100 mg per 7 ggi.
Clotrimazolo candelette vaginali 100 mg, 1 x 2/die
per 3 giorni.
Clotrimazolo candelette vaginali 500 mg, 1 singola
Miconazolo crema 2% (5g) appl. Intravag. per 7gg.
Miconazolo 200 mg ovuli, 1 ovulo per 3 giorni.
Miconazolo 100 mg ovuli, 1 ovulo per 7 giorni.
Nistatina candelette vaginale 100,000 U, per 14 gg
Tioconazolo 6.5% (5 g) appl. intravaginale singola
Terconazolo 0.4% (5 g) appl. intravaginale per 7 gg
89. La Candida, in quanto
fungo,
è indifferente ai
trattamenti con
antibiotici-
Semmai viene favorita da
questi perchè vengono
liberate nicchie
ecologiche e create le
premesse per una
disbiosi
92. Candida albicans è un normale
abitante del nostro sistema digestivo.
E’ presente in proporzioni molto
piccole rispetto ad altri simbionti e non
causa sintomi specifici.
Un certo numero di fattori
predisponenti, molto spesso legati alla
dieta, possono causare lo sviluppo
selettivo di Candida albicans
nell'intestino.
Candidosi Intestinale
94. Candidosi Intestinale
Le candidiasi croniche sono condizioni che
colpiscono milioni di persone in tutto il mondo,
ma sono paradossalmente poco considerate.
Questa patologia è insidiosa perché non si
accompagna a sintomi particolarmente evidenti,
ma può indebolire il sistema immunitario e
compromettere il potenziale di salute delle
persone affette, con conseguenti disturbi
funzionali.
95. Candidosi Intestinali: Fattori predisponenti
Lo squilibrio della flora intestinale, in
seguito a trattamento con antibiotici, è
uno dei principali fattori predisponenti la
proliferazione della Candida.
Tutti gli antibiotici sono implicati e alcuni
(Tetracicline) hanno anche un effetto
stimolante diretto sulla Candida.
96. Le cause principali sono legate al regime dietetico:
Un’alimentazione ricca di zuccheri raffinati; la Candida ama lo
zucchero. E’ in grado di produrre peptidi che attraversano la barriera
intestinale ed emato-encefalica che stimolano la voglia di zucchero.
Tutti i tipi di zucchero sono coinvolti; i frutti dolci, l’eccesso di prodotti
lattiero-caseari fermentati, di grassi saturi, possono alterare l’equilibrio
della microflora intestinale.
Numerosi farmaci, non solo gli antibiotici ma anche corisonici, la pillola
anticoncezionale, gli inibitori di pompa protonica di uso così frequente
per il trattamento di gastriti e Gerd
La sovralimentazione in generale e in particolare quando le capacità
digestine sono alterate
Cattiva digestione: gastrite atrofica, ipocloridria etc
Candidosi Intestinali: Fattori predisponenti
97. • Infezioni da funghi della pelle e delle unghie
• Stanchezza, affaticamento cronico o fibromialgia
• Disturbi funzionali intestinali come gonfiore, o alterazioni alvo
• Malattie autoimmuni quali la tiroidite di Hashimoto, l'artrite
reumatoide, la colite ulcerosa, il lupus, la psoriasi, la
scleroderma o la sclerosi multipla
• Difficoltà di concentrazione e di memorizzazione
• Eczemi, esacerbazione della psoriasi, orticaria e rash
• Irritabilità, alterazioni dell'umore, ansia o depressione
• Infezioni vaginali, infezioni del tratto urinario, prurito rettale o
prurito vaginale
• Allergie stagionali, febbre da fieno, riniti allergiche
• Desiderio smodato di zuccheri e carboidrati
Candidosi Intestinale: 10 sintomi più comuni
98. La Candida produce almento 35 tossine
conosciute: la più conosciuta è la candidina
(la più neurotossica)
- Le tossine alterano la funzione cerebrale.
- Alterano la funzione immunitaria
Nel medio termine provocano alterazioni
sistemiche che coinvolgono diversi sistemi.
Candidosi : Patogenesi e tossicità
99. Le candida produce acetaldeide.
L’ acetaldeide reagisce con un neurotrasmettitore del cervello, la
dopamina, causando sintomi a carico del SNC e disturbi dell’umore e
del comportamento come:
depressione,
ansia e attacchi di panico,
irritabilità,
sbalzi d’umore,
difficoltà di concentrazine e di memorizzazione
Candidosi Intestinale: Patogenesi
103. Immediato senso di gonfiore
intestinale subito dopo il
pasto.
La colite intestinale è
probabilmente il sintomo più
comune e probabilmente il
più banale, della candidosi
cronica.
Disturbi funzionali intestinali cronicizzanti
Candidosi Intestinale: Patogenesi
104. • Gonfiore
• Produzione di gas
• Flatulenza
• Tensione della parete
addominale
• Alterazioni del transito
• Pirosi
• Gerd
Candidosi Intestinale:
disturbi funzionali intestinali
105. La candida aumenta la
permeabilità intestinale.
Una alterazione della
permeabilità facilita il transito
di molecole allergizzanti che
provocano effetti sistemici
dismetabolici
Candidosi Intestinale: Patogenesi
106. Disturbi neurofuzionali per carenza di minerali
Ipereccitabilità neuromuscolare
Disturbi del SNC da tossine
Depressione
Emicrania
Allergie per alterazione della risposta immunitaria umorale
Orticaria
Eczemi
Asma e ipersensibilità chimica multipla
Candidosi Intestinale:
disturbi extra-digestivi
107. La candida può migrare dal tubo digestivo e
aggredire l’apparato genitale e la pelle
• Mughetto
• Eczema micotico del cuoio capelluto,
ascelle, torace.
•Eczema micotico perianale
•Candidosi dell’apparato uro-genitale
108. Vaginite da Candida albicans
Le infezioni fungine dei piedi e
delle unghie dei piedi sono di
solito secondarie all’eccessivo
sviluppo del fungo nel tratto
digestivo.
113. Candidosi: diagnostica di laboratorio
-Coprocultura (esame delle feci, spesso negativo)
- IgG, IgA and IgM anticorpi specifici per Candida
Molti falsi negativi per la capacità immunosoppressive del lievito
- Ematocrito completo
Si può riscontrare aumento dei leucociti o un pattern di riduzione
nei leucociti e aumento dei neutrofili Il calo dei linfociti T4 (CD4) associato ad un
calo del rapporto tra linfociti T4/ linfociti t( (CD4/CD8) attesta la ridotta efficacia dell’immunità cellulare.
-Test dei metaboliti disbiotici nelle urine
La presenza di metaboliti fungini in eccesso (Es. D-Arabinitolo) è
indice di disbiosi e di sovracrescita fungina
-Reattività alla Candidina (principale tossina prodotta dal
lievito)
114. Il trattamento della candidiasi cronica deve essere
protratto meticolosamente per diversi mesi per
ottenere risultati sostenibili.
Il ritorno alle vecchie abitudini alimentari
frequentemente causa ricadute.
Candidosi Intestinale-Trattamento
115. RIDURRE DRASTICAMENTE GLI ZUCCHERI
Evitare cibi ad alto contenuto di carboidrati, zucchero
raffinato (saccarosio, fruttosio), succhi di agrumi, miele,
sciroppo d'acero, frutta in genere, ad eccezione di mele,
ciliegie, frutti di bosco, pere.
Il riso ok perchè viene digerito rapidamente
Limitare il consumo eccessivo di verdure ricche di carboidrati
come patate, mais
AIUTARE LA DIGESTIONE in generale e in particolare
quella DEI CARBOIDRATI se necessario integrando con
enzimi digestivi
Candidosi Intestinale-Trattamento
116. Qualche alimento vietato
Zucchero di canna o raffinato
Miele
Siroppo d’acero
Melasse
Marmellate e gelatine di frutta
Gelati, creme e budini
Bevande zuccherate (gassate e non)
Farine raffinate (pane, pasta biscotti)
Pizza, brioches
Riso bianco raffinato
Fecola di patate
Carote
Mais
Semolino cous cous
Cereali in fiocchi per la colazione
Riso soffiato
Cioccolato non fondente >70%
Candidosi
Intestinale
Trattamento
DIETETICO
DIETA PALEO
AUTOIMMUNE
117. Alimenti accettati
Cereali integrali senza glutine
Pane di miglio
Riso integrale
Fave e farina di fave
Ceci e farina di ceci
Lenticchie
Quore di palma
Pomodoro
Radicchio
Funghi
Carciofi
Insalate verdi
Spinaci
Piselli feschi o secchi
Candidosi
Intestinale
Trattamento
118. Igiene Intestinale
I probiotici sono indispensabili per contrastare lo sviluppo di
Candida, che è inibita da batteri lattici e bifidobatteri della
flora intestinale.
Soprattutto dopo trattamenti ripetuti con antibiotici ripetuti,
la flora è danneggiata e non può esercitare il suo ruolo di
modulazione e di controllo della crescita di agenti patogeni che
possono colonizzare l'intestino.
Diversi ceppi probiotici come il Lactobacillus acidophilus NCFM
e il Saccharomices boulardi hanno dimostrato efficacia
nell'inibire la crescita di Candida.
Il trattamento con probiotici deve essere continuato per mesi.
Candidosi
Intestinale
Trattamento
119. Disturbi funzionali intestinali cronici:
origine fungina o parassitaria
• Approccio?
- Combattere ed eliminare le cause
- Riequilibrare l’ecosistema intestinale
- Agire direttamente sul microbiota con probiotici
- Modifiche dietetiche e dello stile di vita (disbiosi di origine
fungina)
120. Estratti Vegetali ad Azione Antifungina
• Acidi grassi a media catena
l'acido undecenico
l'acido laurico o monolaurina (prodotti come Lauricidin)
• acido caprilico
• Uncaria tomentosa
• Pau d'arco
• Oli essenziali di timo, origano o bergamotto
• Coptide (ranunculacea)
• Tea tre oil
• Semi di pompelmo
• Berberina (da Berberis aristata o Hydrastis)
• Estratti d’aglio (Allicina)
121. Acido caprilico
• L'acido caprilico (nome IUPAC, acido ottanoico) è un acido
carbossilico.
• A temperatura ambiente si presenta come un liquido incolore
dall'odore tenue, corrosivo, oleoso poco solubile in acqua
dall’odore sgradevole (rancido).
• Si trova in natura nella noce di cocco e nel latte materno.
Caprilato di calcio: da acidi grassi a media catena del cocco
- azione antimicotica1
- disturba la produzione della parete cellulare della Candida
- inibisce la proliferazione eccessiva della Candida
122. Acido caprilico e caprico inibiscono la formazione micellare di
candida a bassa concentrazione e sono utilizzabili anche per
uso locale nelle infezioni del cavo orale
123. Il Saccharomices boulardii contrasta la Candida secernendo
acido caprilico e inibisce la sua diffusione
124. Berberis aristata DC
La berberina, utilizzata da secoli nelle medicine tradizionali per
numerose finalità.
La sua azione più conosciuta e di contribuire alla regolazione del
metabolismo del colesterolo. Azione supportata da numerosi
studi clinici.
• La berberina può inoltre supportare lo sviluppo di
microrganismi non patogeni simbionti nel nostro intestino e
contribuire ad una normale funzione dell’apparato GI **
Berberis aristata DC Estratto secco di corteccia
Titolato in berberina (>95%)
- supporta lo sviluppo di microrganismi non patogeni simbionti nel nostro
intestino
- contribuisce ad una normale funzione dell’apparato gastrointestinale
- inibisce la acil-CoA: sterol aciltrasferasi di Candida albicans3
125.
126. La berberina è un alcaloide presente in numerose specie vegetali e in particolar modo nel
genere Berberis.
Nuove evidenze mostrano un’attività della berberina su Candida albicans.
La berberina:
- -provoca aumento della permeabilità di membrana e depolarizzazione della membrana
cellulare in colture di Candida
- Inibisce la trasformazione di Candida in forma di ife (che invadono altri tessuti)
- Azione sinergica con anfotericina, miconazolo e fluconazolo
- Lo studio ha confermato un’azione anti candida e stabilito MIC 17.75 μg/mL
- La berberina può indurre apoptosi nella Candida per aumento dei ROS
- La berberina induce un cambiamento nel metabolismo degli steroli in Candida inibendo la
produzione di ergosterolo
127. Attività della berberina da sola e in combinazione con ampicillina contro Stafilococco
aureus resistente alla meticillina
128. Attività antimicrobiche (verso i batteri) della berberina
- Inibizione della produzione di biofilm batterici in fase di ADESIONE E DI
STABILIZZAZIONE (legame con proteine beta amiloidi del biofilm)
129.
130.
131. Semi di pompelmo
• L’estratto di semi di Pompelmo è ricavato dai semi e dalle
membrane del frutto disidratato.
• I flavanoni presenti in elevata concentrazione influenzano la
funzionalità di membrana di numerosi batteri. In questo modo
l’estratto ha un’azione sull’equilibrio microbiotico inibendo la
proliferazione di alcuni ceppi patogeni. Interessante anche
l’attività di sostegno al microcircolo***
* Citrus grandis L. (pompelmo) Estratto secco di semi
- titolato in bioflavonoidi (flavanoni) 50%
- Azione antimicrobica e regolatrice del microbiota intestinale
133. Aglio
• L’allicina è un composto solforato che la pianta di aglio
produce per difendersi dai parassiti come funghi e batteri.
• Il suo caratteristico odore pungente può essere fastidioso
dopo assuzione orale. Per questo motivo la formulazione del
Candex contiene un estratto dearomatizzato.
• L’estratto di aglio ha una funzione digestiva e antiossidante*
Allium sativum L. (aglio) Estratto secco di bulbi
titolato in allicina (1%)
- azione antibatterico, antielmintica, antimicotica e
antisaccaromiceti4
134.
135.
136. Scanning electron
microscopy pictures of
growing UPEC CFT073
biofilm. Biofilm
architecture was
investigated via SEM in the
presence or absence of
allicin. The images were
untreated control (A) or
treated with 12 µg/mL (B);
25 µg/mL (C); and 50
µg/mL (D) of allicin
137.
138.
139. Origano
• L’estratto secco di Origanum contiene sostanze volatili
aromatiche prodotte dalla pianta per difendersi da parassiti
come batteri e funghi. Contribuisce alla normale regolarità
intestinale e all’eliminazione di gas ****
Origano (estratto secco di foglia)
ricco in carvacrolo e timololo
Inibisce la proliferazione eccessiva della Candida
140.
141.
142. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
143. Commensal Fungi in Health and Disease
FUNGAL COMMUNITIES IN HEALTHY CONDITIONS
ARE DIFFERENT THAN IN DISEASE CONDITIONS
Mucor spp. were specifically noted as more prevalent in
non-obese controls compared to obese subjects, and the
decreased relative abundance of Mucor in obese
subjects was reversed when patients lost weight.
It is uncertain whether these mycobiota changes are
simply a marker for obesity or whether fungal dysbiosis
can actually contribute to the pathogenesis of obesity.
If the latter is true, this could suggest that the mycobiota
may be a potential therapeutic target to combat obesity
and related metabolic disorders.
147. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
150. Dott. Maurizio Salamone Sett-2018
Human Gut Mycobiota
• Human Gut Mycobiota
• Classification of the most important genera (resident and transient)
• Interactions with host, bacterial community
• From mutualism to fulminant pathogenicity
• Fungal metabolites of clinical and diagnostic interest
• Mycobiota and immune system
• Mycobiota and the diet
• Equilibrium of the intestinal ecosystem FGID's and MICI
• Probiotic action of Saccharomices boulardii
• Candida albicans and candidiasis
• Mucor sp., how little we know about you..
• Saccharomyces cerevisiae, other yeasts and molds
• Overview of drug therapy in fungal overgrowths
157. La grande famiglia
dei disinfettanti intestinali
• Antibiotici sistemici
- metronidazolo, macrolidi, fluorchinolonici, ciclosporine
• Antibiotici ad azione locale
- Rifaximina, vancomicina
• Batteriostatici
– Bacitracina, neomicina
• Antimicotici
– Nistatina, fluconazolo, metroimidazolo
• Ecomodulatori intestinali
– Miscele di sostanze naturali in grado di
modularela presenza relativa di gruppi di
simbionti (con azione antimicrobica leggera)
158. Evidenze cliniche per un approccio sinergico con
estratti vegetali
104 Pazienti trattati con rifaximina o estratti di piante per 4 settimane
Gli estratti vegetali di Metagenics erano efficaci e meglio tollerati di rifaximina 1,2g/die in
pazienti con SIBO (positivi al breath test con lattulosio)
Successo terapeutico in 17 su 37 (46%) rispetto ai 23/67 di rifaximina (34%)
Minori effetti indesiderati nel gruppo con estratti vegetali (meno diarrea).
159. La presa in carico del paziente in medicina
funzionale con la strategia delle 4R
Rimuovere Le cause di squilibrio
dell’ecosistema intestinale
1. Parassiti (elminti)
2. Microbi patogeni
3. Allergeni alimentari
4. Nutrienti in eccesso
5. Alcool e tossici xenobionti
Rimpiazzare Quello che manca per una
corretta digestione
1. Enzimi digestivi
2. Sali biliari
3. Modulazione acidità
gastrica
Reinoculare Simbionti probiotici
preparando loro il terreno
Probiotici
Lactobacillus acidophilus NCFM,
Bifidobacterium lactis Bl-07 NH019 Saccharomices
boulardii
Prebiotici (fos e inuline)
Riparare Mantenere la salute degli
enterociti e la funzione di
barriera intestinale
Glutammina, vitamine,
minerali, antiossidanti
curcumina, quercetina
161. Contatti: msal37@gmail.com +39 3663461468
https://www.linkedin.com/in/mauriziosalamone
http://www.slideshare.net/Maurizio37
https://www.facebook.com/maurizio.salamone
Maurizio Salamone, biologist
Science Manager - Metagenics Italia srl.
Società Internazionale di Neuropsicocardiologia
Disclaimer:
Maurizio Salamone is a Metagenics Italia srl employe