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Article ; Online: Trust the gut: Outcomes of gut microbiota transplant in metabolic and cognitive disorders.

Guzzardi, Maria Angela / La Rosa, Federica / Iozzo, Patricia

2023 Volume 149, Page(s) 105143

Abstract: Type 2 diabetes mellitus (T2DM) is a main public health concern, with increasing prevalence and growingly premature onset in children, in spite of emerging and successful therapeutic options. T2DM promotes brain aging, and younger age at onset is ... ...

Abstract	Type 2 diabetes mellitus (T2DM) is a main public health concern, with increasing prevalence and growingly premature onset in children, in spite of emerging and successful therapeutic options. T2DM promotes brain aging, and younger age at onset is associated with a higher risk of subsequent dementia. Preventive strategies should address predisposing conditions, like obesity and metabolic syndrome, and be started from very early and even prenatal life. Gut microbiota is an emerging target in obesity, diabetes and neurocognitive diseases, which could be safely modulated since pregnancy and infancy. Many correlative studies have supported its involvement in disease pathophysiology. Faecal material transplantation (FMT) studies have been conducted in clinical and preclinical settings to deliver cause-effect proof and mechanistic insights. This review provides a comprehensive overview of studies in which FMT was used to cure or cause obesity, metabolic syndrome, T2DM, cognitive decline and Alzheimer's disease, including the evidence available in early life. Findings were analysed to dissect consolidated from controversial results, highlighting gaps and possible future directions.
MeSH term(s)	Child ; Humans ; Metabolic Syndrome/therapy ; Gastrointestinal Microbiome/physiology ; Diabetes Mellitus, Type 2/therapy ; Trust ; Obesity/therapy ; Cognitive Dysfunction/therapy
Language	English
Publishing date	2023-03-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2023.105143
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Article: Artificial Intelligence Algorithms for Benign vs. Malignant Dermoscopic Skin Lesion Image Classification.

Brutti, Francesca / La Rosa, Federica / Lazzeri, Linda / Benvenuti, Chiara / Bagnoni, Giovanni / Massi, Daniela / Laurino, Marco

Bioengineering (Basel, Switzerland)

2023 Volume 10, Issue 11

Abstract: In recent decades, the incidence of melanoma has grown rapidly. Hence, early diagnosis is crucial to improving clinical outcomes. Here, we propose and compare a classical image analysis-based machine learning method with a deep learning one to ... ...

Abstract	In recent decades, the incidence of melanoma has grown rapidly. Hence, early diagnosis is crucial to improving clinical outcomes. Here, we propose and compare a classical image analysis-based machine learning method with a deep learning one to automatically classify benign vs. malignant dermoscopic skin lesion images. The same dataset of 25,122 publicly available dermoscopic images was used to train both models, while a disjointed test set of 200 images was used for the evaluation phase. The training dataset was randomly divided into 10 datasets of 19,932 images to obtain an equal distribution between the two classes. By testing both models on the disjoint set, the deep learning-based method returned accuracy of 85.4 ± 3.2% and specificity of 75.5 ± 7.6%, while the machine learning one showed accuracy and specificity of 73.8 ± 1.1% and 44.5 ± 4.7%, respectively. Although both approaches performed well in the validation phase, the convolutional neural network outperformed the ensemble boosted tree classifier on the disjoint test set, showing better generalization ability. The integration of new melanoma detection algorithms with digital dermoscopic devices could enable a faster screening of the population, improve patient management, and achieve better survival rates.
Language	English
Publishing date	2023-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering10111322
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Article ; Online: Evidence of a Gastro-Duodenal Effect on Adipose Tissue and Brain Metabolism, Potentially Mediated by Gut-Liver Inflammation: A Study with Positron Emission Tomography and Oral

Guzzardi, Maria Angela / La Rosa, Federica / Campani, Daniela / Cacciato Insilla, Andrea / Nannipieri, Monica / Brunetto, Maurizia Rossana / Bonino, Ferruccio / Iozzo, Patricia

International journal of molecular sciences

2022 Volume 23, Issue 5

Abstract: Interventions affecting gastrointestinal (GI) physiology suggest that the GI tract plays an important role in modulating the uptake of ingested glucose by body tissues. We aimed at validating the use of positron emission tomography (PET) with ... ...

Abstract	Interventions affecting gastrointestinal (GI) physiology suggest that the GI tract plays an important role in modulating the uptake of ingested glucose by body tissues. We aimed at validating the use of positron emission tomography (PET) with oral
MeSH term(s)	Adipose Tissue/diagnostic imaging ; Adipose Tissue/metabolism ; Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Fluorodeoxyglucose F18/metabolism ; Glucose/metabolism ; Hepatitis/metabolism ; Inflammation/diagnostic imaging ; Inflammation/metabolism ; Lipids ; Mice ; Positron-Emission Tomography
Chemical Substances	Lipids ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23052659
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Article ; Online: Gut-derived metabolites mediating cognitive development in 5-year-old children: Early-life transplant in mice has lasting effects throughout adulthood.

Guzzardi, Maria Angela / La Rosa, Federica / Granziera, Federico / Panetta, Daniele / Pardo-Tendero, Mercedes / Barone, Monica / Turroni, Silvia / Faita, Francesco / Kusmic, Claudia / Brigidi, Patrizia / Monleon, Daniel / Iozzo, Patricia

Brain, behavior, and immunity

2023 Volume 114, Page(s) 94–110

Abstract: The gut microbiota has been causally linked to cognitive development. We aimed to identify metabolites mediating its effect on cognitive development, and foods or nutrients related to most promising metabolites. Faeces from 5-year-old children (DORIAN- ... ...

Abstract	The gut microbiota has been causally linked to cognitive development. We aimed to identify metabolites mediating its effect on cognitive development, and foods or nutrients related to most promising metabolites. Faeces from 5-year-old children (DORIAN-PISAC cohort, including 90 general population families with infants, 42/48 females/males, born in 2011-2014) were transplanted (FMT) into C57BL/6 germ-free mice. Children and recipient mice were stratified by cognitive phenotype, or based on protective metabolites. Food frequency questionnaires were obtained in children. Cognitive measurements in mice included five Y-maze tests until 23 weeks post-FMT, and (at 23 weeks) PET-CT for brain metabolism and radiodensity, and ultrasound-based carotid vascular indices. Children (faeces, urine) and mice (faeces, plasma) metabolome was measured by 1H NMR spectroscopy, and the faecal microbiota was profiled in mice by 16S rRNA amplicon sequencing. Cognitive scores of children and recipient mice were correlated. FMT-dependent modifications of brain metabolism were observed. Mice receiving FMT from high-cognitive or protective metabolite-enriched children developed superior cognitive-behavioural performance. A panel of metabolites, namely xanthine, hypoxanthine, formate, mannose, tyrosine, phenylalanine, glutamine, was found to mediate the gut-cognitive axis in donor children and recipient mice. Vascular indices partially explained the metabolite-to-phenotype relationships. Children's consumption of legumes, whole-milk yogurt and eggs, and intake of iron, zinc and vitamin D appeared to support protective gut metabolites. Overall, metabolites involved in inflammation, purine metabolism and neurotransmitter synthesis mediate the gut-cognitive axis, and holds promise for screening. The related dietary and nutritional findings offer leads to microbiota-targeted interventions for cognitive protection, with long-lasting effects.
Language	English
Publishing date	2023-08-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.08.009
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Maturation of the Visceral (Gut-Adipose-Liver) Network in Response to the Weaning Reaction versus Adult Age and Impact of Maternal High-Fat Diet

Guzzardi, Maria Angela / La Rosa, Federica / Campani, Daniela / Cacciato Insilla, Andrea / De Sena, Vincenzo / Panetta, Daniele / Brunetto, Maurizia Rossana / Bonino, Ferruccio / Collado, Maria Carmen / Iozzo, Patricia

Nutrients. 2021 Sept. 28, v. 13, no. 10

2021

Abstract: Metabolic-associated fatty liver disease is a major cause of chronic pathologies, of which maternal obesity is a frequent risk factor. Gut wall and microbiota, visceral fat, and liver form a pre-systemic network for substrates and pro-inflammatory ... ...

Abstract	Metabolic-associated fatty liver disease is a major cause of chronic pathologies, of which maternal obesity is a frequent risk factor. Gut wall and microbiota, visceral fat, and liver form a pre-systemic network for substrates and pro-inflammatory factors entering the body, undergoing accelerated maturation in early-life when the weaning reaction, i.e., a transitory inflammatory condition, affects lifelong health. We aimed to characterize organ metabolism in the above network, in relation to weaning reaction and maternal obesity. Weaning or 6-months-old offspring of high-fat-diet and normal-diet fed dams underwent in vivo imaging of pre-/post-systemic glucose uptake and tissue radiodensity in the liver, visceral fat, and intestine, a liver histology, and microbiota and metabolic pathway analyses. Weaning mice showed the dominance of gut Clostridia and Bacteroidia members, overexpressing pathways of tissue replication and inflammation; adulthood increased proneness to steatohepatitis, and Desulfovibrio and RF39 bacteria, and lipopolysaccharide, bile acid, glycosaminoglycan, and sphingolipid metabolic pathways. In vivo imaging could track organ maturation, liver inflammation, and protective responses. A maternal high-fat diet amplified the weaning reaction, elevating liver glucose uptake, triglyceride levels, and steatohepatitis susceptibility along the lifespan. The visceral network establishes a balance between metabolism and inflammation, with clear imaging biomarkers, and crucial modulation in the weaning time window.
Keywords	Bacteroidia ; Clostridia ; Desulfovibrio ; adulthood ; adults ; bile acids ; biochemical pathways ; biomarkers ; fatty liver ; glucose ; glycosaminoglycans ; high fat diet ; histology ; inflammation ; intestines ; lipopolysaccharides ; liver ; longevity ; metabolism ; obesity ; progeny ; risk factors ; sphingolipids ; triacylglycerols ; visceral fat
Language	English
Dates of publication	2021-0928
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13103438
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients.

European journal of clinical investigation

2024 , Page(s) e14235

Abstract: Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV ... ...

Abstract	Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies. Methods: The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis. Results: During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HR Conclusions: PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.
Language	English
Publishing date	2024-05-11
Publishing country	England
Document type	Journal Article
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.14235
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Article: Liver and White/Brown Fat Dystrophy Associates with Gut Microbiota and Metabolomic Alterations in 3xTg Alzheimer's Disease Mouse Model.

Guzzardi, Maria Angela / La Rosa, Federica / Campani, Daniela / Collado, Maria Carmen / Monleon, Daniel / Cacciato Insilla, Andrea / Tripodi, Maria / Zega, Alessandro / Dattilo, Alessia / Brunetto, Maurizia Rossana / Maffei, Margherita / Bonino, Ferruccio / Iozzo, Patricia

Metabolites

2022 Volume 12, Issue 4

Abstract: Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer's disease (AD), highlighting the role of the liver-adipose-tissue-brain axis in AD pathophysiology. The gut microbiota might play a modulating role. ... ...

Abstract	Metabolic impairments and liver and adipose depots alterations were reported in subjects with Alzheimer's disease (AD), highlighting the role of the liver-adipose-tissue-brain axis in AD pathophysiology. The gut microbiota might play a modulating role. We investigated the alterations to the liver and white/brown adipose tissues (W/BAT) and their relationships with serum and gut metabolites and gut bacteria in a 3xTg mouse model during AD onset (adulthood) and progression (aging) and the impact of high-fat diet (HFD) and intranasal insulin (INI). Glucose metabolism (
Language	English
Publishing date	2022-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo12040278
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Article: Maternal High-Fat Feeding Affects the Liver and Thymus Metabolic Axis in the Offspring and Some Effects Are Attenuated by Maternal Diet Normalization in a Minipig Model.

La Rosa, Federica / Guiducci, Letizia / Guzzardi, Maria Angela / Cacciato Insilla, Andrea / Burchielli, Silvia / Brunetto, Maurizia Rossana / Bonino, Ferruccio / Campani, Daniela / Iozzo, Patricia

Metabolites

2021 Volume 11, Issue 12

Abstract: Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their ... ...

Abstract	Maternal high-fat diet (HFD) affects metabolic and immune development. We aimed to characterize the effects of maternal HFD, and the subsequent diet-normalization of the mothers during a second pregnancy, on the liver and thymus metabolism in their offspring, in minipigs. Offspring born to high-fat (HFD) and normal diet (ND) fed mothers were studied at week 1 and months 1, 6, 12 of life. Liver and thymus glucose uptake (GU) was measured with positron emission tomography during hyperinsulinemic-isoglycemia. Histological analyses were performed to quantify liver steatosis, inflammation, and hepatic hematopoietic niches (HHN), and thymocyte size and density in a subset. The protocol was repeated after maternal-diet-normalization in the HFD group. At one week, HFD
Language	English
Publishing date	2021-11-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo11120800
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Article ; Online: Maturation of the Visceral (Gut-Adipose-Liver) Network in Response to the Weaning Reaction versus Adult Age and Impact of Maternal High-Fat Diet.

Nutrients

2021 Volume 13, Issue 10

Abstract	Metabolic-associated fatty liver disease is a major cause of chronic pathologies, of which maternal obesity is a frequent risk factor. Gut wall and microbiota, visceral fat, and liver form a pre-systemic network for substrates and pro-inflammatory factors entering the body, undergoing accelerated maturation in early-life when the weaning reaction, i.e., a transitory inflammatory condition, affects lifelong health. We aimed to characterize organ metabolism in the above network, in relation to weaning reaction and maternal obesity. Weaning or 6-months-old offspring of high-fat-diet and normal-diet fed dams underwent in vivo imaging of pre-/post-systemic glucose uptake and tissue radiodensity in the liver, visceral fat, and intestine, a liver histology, and microbiota and metabolic pathway analyses. Weaning mice showed the dominance of gut
MeSH term(s)	Adipose Tissue/metabolism ; Age Factors ; Animals ; Biomarkers ; Diet, High-Fat ; Disease Susceptibility ; Energy Metabolism ; Feedback, Physiological ; Female ; Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism ; Immunohistochemistry ; Liver/metabolism ; Maternal Nutritional Physiological Phenomena ; Metabolic Networks and Pathways ; Mice ; Organ Specificity ; Positron Emission Tomography Computed Tomography ; Pregnancy ; Prenatal Exposure Delayed Effects ; Weaning
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13103438
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Article ; Online: Leptin resistance before and after obesity: evidence that tissue glucose uptake underlies adipocyte enlargement and liver steatosis/steatohepatitis in Zucker rats from early-life stages.

Guzzardi, Maria Angela / Guiducci, Letizia / Campani, Daniela / La Rosa, Federica / Cacciato Insilla, Andrea / Bartoli, Antonietta / Cabiati, Manuela / De Sena, Vincenzo / Del Ry, Silvia / Burchielli, Silvia / Bonino, Ferruccio / Iozzo, Patricia

International journal of obesity (2005)

2021 Volume 46, Issue 1, Page(s) 50–58

Abstract: Background: Leptin resistance occurs in obese patients, but its independent contribution to adiposity and the accompanying metabolic diseases, i.e., diabetes, liver steatosis, and steatohepatitis, remains to be established. This study was conducted in ... ...

Abstract	Background: Leptin resistance occurs in obese patients, but its independent contribution to adiposity and the accompanying metabolic diseases, i.e., diabetes, liver steatosis, and steatohepatitis, remains to be established. This study was conducted in an extreme model of leptin resistance to investigate mechanisms initiating diabetes, fat expansion, liver steatosis, and inflammatory disease, focusing on the involvement of glucose intolerance and organ-specific glucose uptake in brown and subcutaneous adipose tissues (BAT, SAT) and in the liver. Methods: We studied preobese and adult Zucker rats (fa/fa, fa/+ ) during fasting or glucose loading to assess glucose tolerance. Relevant pancreatic and intestinal hormonal levels were measured by Milliplex. Imaging of Results: Preobese fa/fa pups showed impaired glucose tolerance, adipocyte enlargement, hepatic microsteatosis, and lobular inflammation, with elevated hepatic post-glucose load glucose uptake and production. Adult fa/fa rats had more severe glucose intolerance, fasting hyperglycemia, hormonal abnormalities, elevated glucose uptake in SAT and BAT, and more markedly in the liver, together with macrosteatosis, and highly prevalent hepatic inflammation. Organ glucose uptake was proportional to the degree of fat accumulation and tissue inflammation and was able to dissect healthy from NAFLD and NAFLD/NASH livers. Most severe NASH livers showed a decline in glucose uptake and liver enzymes. Conclusions: In fa/fa Zucker rats, leptin resistance leads to glucose intolerance, mainly due to hepatic glucose overproduction, preceding obesity, and explaining pancreatic and intestinal hormonal changes and fat accumulation in adipocytes and hepatocytes. Our data support the involvement of liver glucose uptake in the pathogenesis of liver inflammatory disease. Its potential as more generalized biomarker or diagnostic approach remains to be established outside of our leptin-receptor-deficient rat model.
MeSH term(s)	Adipocytes/metabolism ; Adipocytes/physiology ; Animals ; Disease Models, Animal ; Fatty Liver/complications ; Fatty Liver/metabolism ; Glucose/analysis ; Leptin/metabolism ; Obesity/blood ; Obesity/complications ; Rats ; Rats, Zucker/abnormalities ; Rats, Zucker/metabolism
Chemical Substances	Leptin ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752409-2
ISSN	1476-5497 ; 0307-0565
ISSN (online)	1476-5497
ISSN	0307-0565
DOI	10.1038/s41366-021-00941-z
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