8openItalian coauthor/editoropenMancini, A.; Larsen, S.; Campagna, F.; Franceschi, P.; Amodio, P.; Pravadelli, C.; Pindo, M; Tuohy, K.Mancini, A.; Larsen, S.; Campagna, F.; Franceschi, P.; Amodio, P.; Pravadelli, C.; Pindo, M.; Tuohy, K

Amodio, P.

Campagna, F.

Franceschi, P.

Larsen, S.

Mancini, A.

Pindo, M.

Pravadelli, C.

Tuohy, K.

English

Gut microbiota has a fundamental role in the pathogenesis of liver cirrhosis as well as their complications as in the case of hepatic encephalopathy (HE). HE is a spectrum of neurocognitive impairments with a complex pathogenesis, where ammonia and other gut microbiota by-products have a fundamental role in its development. Current HE clinical treatment is mainly based on manipulating the gut microbiota and ammonia production/absorption using prebiotic lactulose, antibiotic rifaximin and probiotic VSL#3. Here we investigated the modulation of gut microbiota, in terms of microbial composition and metabolism, upon fermentation of lactulose, rifaximin and VSL#3, using in vitro anaerobic pH-controlled batch cultures inoculated with faecal microbiota of cirrhotic patients.
In vitro fermentations were perfomed over 24 hours. Flow cytometry (FISH/FCM) was used to accurately enumerate different bacterial species and genera, while bacterial microbiota community structure was analysed using high-throughput sequencing of the 16S rRNA gene. Modification in ammonia concentration and SCFA content were determined across the experiments.
Over time, cirrhotic microbiota responded dynamically to the treatments. In particular, significant differences (PERMANOVA Weighted/Unweighted/Bray-Curtis estimators) were observed after 24h. The main taxa associated with decompensated cirrhosis, were reduced with lactulose. At the same time, taxa associated with healthy conditions, such as Lachnospiraceae, Ruminococcaceae, Blautia, Bifidobacterium and Faecalibacterium, were promoted as confirmed by the Indicator Species Analysis. Lactulose alone or in combination with the probiotic VSL#3 led to an increase production of SCFA and decrease in ammonia production. These shifts in metabolite production are indicative of carbohydrate fermentation and are consistent with improved gut health and reduced risk of HE.
We demonstrated that lactulose is able to significantly increase the relative abundance and absolute numbers of bifidobacteria, which was associated with an increased production of SCFA and a reduction in ammonia content. Future investigations should assess the molecular pathways that are involved in the modulation of gut microbiota and its metabolic reprogramming while translational studies should examine the clinical potential of this in vitro observations

Archivio istituzionale della ricerca - Fondazione Edmund Mach

Prebiotic lactulose as efficacious microbiota and metabolite modulator in cirrhosis environment

Pindo, M

33ORAL COMMUNICATIONS  ORAL COMMUNICATIONSPREBIOTIC LACTULOSE AS EFFICACIOUS MICROBIOTA AND METABOLITE MODULATOR IN CIRRHOSIS ENVIRONMENT Andrea Mancini (1) - Stefano Larsen (2) - Francesca Campagna (3) - Pietro Franceschi (2) - Piero Amodio (3) - Cecilia Pravadelli (4) - Massimo Pindo (5) - Kieran Tuohy (1)Fondazione Edmund Mach, Food Quality and Nutrition, San Michele all’Adige, Italy (1) - Fondazione Edmund Mach, Computational Biology Unit, San Michele all’Adige, Italy (2) - University of Padova, Department of Medicine-DIMED, Padova, Italy (3) - Santa Chiara Hospital, Gastroenterology Unit, Trento, Italy (4) - Fondazione Edmund Mach, Computational biology unit, San Michele all’Adige, Italy (5)Objective:Gut microbiota has a fundamental role in the pathogenesis of liver cirrhosis as well as their complications as in the case of hepatic encephalopathy (HE). Current HE clinical treatment is mainly based on manipulating the gut microbiota and ammonia production/absorption using prebiotic lactulose, antibiotic rifaximin and probiotic VSL#3. Methods:Here we investigated the modulation of gut microbiota, in terms of microbial composition and metabolism, upon fermentation of lactulose, rifaximin and VSL#3, using in vitro-24hours anaerobic pH-controlled batch cultures inoculated with faecal microbiota of cirrhotic patients. Results:Over time, cirrhotic microbiota responded dynamically to the treatments. In particular, significant differences (PERMANOVA Weighted/Unweighted/Bray-Curtis estimators) were observed after 24h. The main taxa associated with decompensated cirrhosis, were reduced with lactulose. At the same time, taxa associated with healthy conditions, such as Lachnospiraceae, Ruminococcaceae, Blautia and Bifidobacterium, were promoted as confirmed by the Indicator Species Analysis. Lactulose alone or in combination with the probiotic VSL#3 led to an increase production of SCFA and decrease in ammonia production. These shifts in metabolite production are indicative of carbohydrate fermentation and are consistent with improved gut health and reduced risk of HE. Conclusions:We demonstrated that lactulose is able to significantly increase the relative abundance and absolute numbers of bifidobacteria, which was associated with an increased production of SCFA and a reduction in ammonia content. Future investigations should assess the molecular pathways that are involved in the modulation of gut microbiota and its metabolic reprogramming while translational studies should examine the clinical potential of this in vitro observations.BIOCHEMICAL AND ANTIBIOTIC INFLUENCE OF GASTROINTESTINAL TRACTS MICROFLORA IN NEONATAL Awatif Al-Judaibi (1) - Effat AlJudaibi (2) - Sahar AlShareef (2)Jeddah University, Biological Science, Microbiology Section, Jeddah, Saudi Arabia (1) - Jeddah University, Biological Science, Jeddah, Saudi Arabia (2)Objective: Colonisation of the neonatal intestinal tract by microbiota may occur as early as the foetal stage, and this colonisation preforms the intestinal microbiota, which is reflected in the intestinal activity and neonate vitality. This study aimed to isolate and identify common bacteria in 19 preterm neonates spending their first weeks of life in the neonatal intensive care unit. Methods: First, stool samples were collected, and bacteria were isolated and purified from those samples.Common bacterial species were investigated regarding their susceptibility or resistance to antibiotics. From 19 stool samples, 15 contained three species in common: Enterobacter cloacae, Enterococcus faecalis and Klebsiella pneumoniae.Results: Differences in the microbial formation and density were correlated with the type of delivery and feeding as well as the administration or no administration of antibiotics to the preterm neonate. Antibiotic susceptibility testing was undertaken, and minimum inhibitory concentrations were determined. The results showed that the minimum level of isolates was affected by several of the most commonly used antibiotics from the following families: aminoglycosides, carbapenems, fluroquinolones, glycylcyclines and polymyxins.Conclusions: In the present study, we identified the most common bacterial species present in the intestinal microflora of premature infants during their first days after birth. Enterobacter cloacae and Klebsiella pneumoniae were the most common gram-negative bacteria, while Enterococcus faecalis was the most prevalent gram-positive bacterium. Our microbial susceptibility testing showed that these isolates were sensitive to several of the most commonly used antibiotics from the following families: aminoglycosides, carbapenems, fluroquinolones, glycylcyclines and polymyxins. The analysis revealed a significant level of sensitive towards most tested antibiotics among certain strains isolated from neonates, which raises concern.

https://openpub.fmach.it/bitstream/10449/71242/3/2021%2011th%20Prebiotics_Mancini%2033.pdf

Prebiotic lactulose as efficacious microbiota and metabolite modulator in cirrhosis environment

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Archivio istituzionale della ricerca - Fondazione Edmund Mach

Archivio istituzionale della ricerca - Fondazione Edmund Mach