The aim of this PhD work was the characterization of the intestinal microbial ecosystem through bioinformatic and statistical analyses of the microbiomics data originated from three studies carried out on different human populations: healthy (non-diseased) adults, hyperlipidemic and normo-lipidemic children and adolescents, and subjects with diagnosed irritable bowel syndrome (IBS). Specifically, the three studies presented in this PhD theses were as follows: • Probiotic crossover intervention study: A randomized, double-blind, crossover, placebo-controlled intervention study was carried out to determine the impact of a Bifidobacterium bifidum strain on the IME of adult healthy volunteers. • Children’s dyslipidemia single arm intervention study: In this trial, the IME of children and adolescents with primary hyperlipidemia (a risk factor for cardiovascular diseases) was compared with the IME of control (normo-lipidemic) group. In addition, the modulatory effect of the regular intake of hazelnuts on hyperlipidemic subjects’s IME was examines in order to evaluate if the modulation of IME by hazelnuts ameliorates the lipid profile. • Irritable bowel syndrome (IBS) observational study: The aim of this trial was the characterization of the IME in human subjects affected by IBS. The characterization was performed through the analysis of the bacterial communities present in the faecal samples collected during a multicentre intervention trial (Cremon et al., 2017). Irritable bowel syndrome is the most common gastrointestinal disorder in western countries. IBS is conventionally classified in four different subtypes based on bowel clinical symptoms: constipation, diarrhoea, alternating constipation and diarrhoea, and unsubtyped IBS. Clinical and immunological data collected during the trial were used to investigate the potential correlations between the IME characteristic for a specific IBS subtypes and the physiological and clinical parameters of the host, including bowel symptoms, faecal levels of IgA and cytokines, and depression/anxiety scores. The analysis of the data collected during the three studies presented in this PhD thesis revealed significant correlations between the intestinal microbial ecosystem and specific physiological parameters, characteristic for the physiological conditions under study. Therefore, these findings suggest that the differential abundance of specific OTUs could be used as a biomarker for a specific host condition. Conclusion of the probiotic B. bifidum Bb crossover intervention trial The intervention trial based on the administration of B. bifidum strain Bb has shown that the probiotic treatment modified the relative abundances of bacterial taxa that have often been associated with healthy conditions. The treatment modulated the faecal levels of butyrate, a microbial metabolite exerting multiple effects on gut health. Therefore, the daily consumption of B. bifidum Bb cells may positively affect human health; however, as for most dietary interventions, the current state of knowledge does not allow us to better define the significance of any taxonomic or metabolite changes of the intestinal microbial ecosystem on the host health. Conclusion of children’s dyslipidemia single arm intervention trial The results of this study support the hypothesis that young individuals with primary hyperlipidemia possess an dysbiotic intestinal microbial ecosystem, which could plausibly contribute to the abnormal lipid profile of these subjects. A limitation of this study is the small sample size, which may reduce the potential robustness of the obtained results. Moreover, further studies focusing on the mechanisms involved in such hypothesized association are warranted. Our study is the first human trial investigating the potential role of hazelnuts as IME modulator and, in specific, suggests that a dietary intervention with hazelnut could be an effective and practical strategy to positively modulate the IME of hyperlipidemic subjects. Conclusion of the IBS-subtypes observational study This descriptive study demonstrates that the altered distribution of bacteria within the Gram-positive order Clostridiales distinguishes the intestinal microbial ecosystem of IBS subtypes, plausibly contributing to the observed altered faecal levels of the SCFAs acetate, butyrate and propionate. Our study proposes intestinal Clostridiales and colonic SCFAs as IBS subtypes biomarkers that can also potentially represent therapeutic targets. In addition, this study supports the notion that distinct therapeutic approaches should be developed for the different IBS subtype.

EVALUATION OF THE IMPACT OF DIETARY INTERVENTIONS ON THE HUMAN INTESTINAL MICROBIAL ECOSYSTEM THROUGH IMPROVED BIOINFORMATICS AND STATISTICS / G. Gargari ; tutor: S. Guglielmetti ; phd dean: F. Bonomi. - : . DIPARTIMENTO DI SCIENZE PER GLI ALIMENTI, LA NUTRIZIONE E L'AMBIENTE, 2017 Dec 21. ((30. ciclo, Anno Accademico 2017. [10.13130/g-gargari_phd2017-12-21].

EVALUATION OF THE IMPACT OF DIETARY INTERVENTIONS ON THE HUMAN INTESTINAL MICROBIAL ECOSYSTEM THROUGH IMPROVED BIOINFORMATICS AND STATISTICS

G. Gargari
2017-12-21

Abstract

The aim of this PhD work was the characterization of the intestinal microbial ecosystem through bioinformatic and statistical analyses of the microbiomics data originated from three studies carried out on different human populations: healthy (non-diseased) adults, hyperlipidemic and normo-lipidemic children and adolescents, and subjects with diagnosed irritable bowel syndrome (IBS). Specifically, the three studies presented in this PhD theses were as follows: • Probiotic crossover intervention study: A randomized, double-blind, crossover, placebo-controlled intervention study was carried out to determine the impact of a Bifidobacterium bifidum strain on the IME of adult healthy volunteers. • Children’s dyslipidemia single arm intervention study: In this trial, the IME of children and adolescents with primary hyperlipidemia (a risk factor for cardiovascular diseases) was compared with the IME of control (normo-lipidemic) group. In addition, the modulatory effect of the regular intake of hazelnuts on hyperlipidemic subjects’s IME was examines in order to evaluate if the modulation of IME by hazelnuts ameliorates the lipid profile. • Irritable bowel syndrome (IBS) observational study: The aim of this trial was the characterization of the IME in human subjects affected by IBS. The characterization was performed through the analysis of the bacterial communities present in the faecal samples collected during a multicentre intervention trial (Cremon et al., 2017). Irritable bowel syndrome is the most common gastrointestinal disorder in western countries. IBS is conventionally classified in four different subtypes based on bowel clinical symptoms: constipation, diarrhoea, alternating constipation and diarrhoea, and unsubtyped IBS. Clinical and immunological data collected during the trial were used to investigate the potential correlations between the IME characteristic for a specific IBS subtypes and the physiological and clinical parameters of the host, including bowel symptoms, faecal levels of IgA and cytokines, and depression/anxiety scores. The analysis of the data collected during the three studies presented in this PhD thesis revealed significant correlations between the intestinal microbial ecosystem and specific physiological parameters, characteristic for the physiological conditions under study. Therefore, these findings suggest that the differential abundance of specific OTUs could be used as a biomarker for a specific host condition. Conclusion of the probiotic B. bifidum Bb crossover intervention trial The intervention trial based on the administration of B. bifidum strain Bb has shown that the probiotic treatment modified the relative abundances of bacterial taxa that have often been associated with healthy conditions. The treatment modulated the faecal levels of butyrate, a microbial metabolite exerting multiple effects on gut health. Therefore, the daily consumption of B. bifidum Bb cells may positively affect human health; however, as for most dietary interventions, the current state of knowledge does not allow us to better define the significance of any taxonomic or metabolite changes of the intestinal microbial ecosystem on the host health. Conclusion of children’s dyslipidemia single arm intervention trial The results of this study support the hypothesis that young individuals with primary hyperlipidemia possess an dysbiotic intestinal microbial ecosystem, which could plausibly contribute to the abnormal lipid profile of these subjects. A limitation of this study is the small sample size, which may reduce the potential robustness of the obtained results. Moreover, further studies focusing on the mechanisms involved in such hypothesized association are warranted. Our study is the first human trial investigating the potential role of hazelnuts as IME modulator and, in specific, suggests that a dietary intervention with hazelnut could be an effective and practical strategy to positively modulate the IME of hyperlipidemic subjects. Conclusion of the IBS-subtypes observational study This descriptive study demonstrates that the altered distribution of bacteria within the Gram-positive order Clostridiales distinguishes the intestinal microbial ecosystem of IBS subtypes, plausibly contributing to the observed altered faecal levels of the SCFAs acetate, butyrate and propionate. Our study proposes intestinal Clostridiales and colonic SCFAs as IBS subtypes biomarkers that can also potentially represent therapeutic targets. In addition, this study supports the notion that distinct therapeutic approaches should be developed for the different IBS subtype.
GUGLIELMETTI, SIMONE DOMENICO
BONOMI, FRANCESCO
Bifidumbacterium bifidum; hyperlipidemia; IBS; SCFAs;microbiota; IME
Settore AGR/16 - Microbiologia Agraria
EVALUATION OF THE IMPACT OF DIETARY INTERVENTIONS ON THE HUMAN INTESTINAL MICROBIAL ECOSYSTEM THROUGH IMPROVED BIOINFORMATICS AND STATISTICS / G. Gargari ; tutor: S. Guglielmetti ; phd dean: F. Bonomi. - : . DIPARTIMENTO DI SCIENZE PER GLI ALIMENTI, LA NUTRIZIONE E L'AMBIENTE, 2017 Dec 21. ((30. ciclo, Anno Accademico 2017. [10.13130/g-gargari_phd2017-12-21].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/541101
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