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1.
Am J Physiol Endocrinol Metab ; 326(2): E166-E177, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38019083

ABSTRACT

Functional hypothalamic amenorrhea (FHA) is characterized by estrogen deficiency that significantly impacts metabolic, bone, cardiovascular, mental, and reproductive health. Given the importance of environmental factors such as stress and body composition, and particularly considering the importance of estrogens in regulating the gut microbiota, some changes in the intestinal microenvironment are expected when all of these factors occur simultaneously. We aimed to assess whether the gut microbiota composition is altered in FHA and to determine the potential impact of hormonal replacement therapy (HRT) on the gut microbiota. This prospective observational study included 33 patients aged 18-34 yr with FHA and 10 age-matched healthy control women. Clinical, hormonal, and metabolic evaluations were performed at baseline for the FHA group only, whereas gut microbiota profile was assessed by 16S rRNA gene amplicon sequencing for both groups. All measurements were repeated in patients with FHA after receiving HRT for 6 mo. Gut microbiota alpha diversity at baseline was significantly different between patients with FHA and healthy controls (P < 0.01). At the phylum level, the relative abundance of Fusobacteria was higher in patients with FHA after HRT (P < 0.01), as was that of Ruminococcus and Eubacterium at the genus level (P < 0.05), which correlated with a decrease in circulating proinflammatory cytokines. FHA is a multidimensional disorder that is interconnected with dysbiosis through various mechanisms, particularly involving the gut-brain axis. HRT appears to induce a favorable shift in the gut microbiota in patients with FHA, which is also associated with a reduction in the systemic inflammatory status.NEW & NOTEWORTHY Our study marks the first comprehensive analysis of gut microbiota composition in FHA and the impact of HRT on it, along with biochemical, anthropometric, and psychometric aspects. Our results indicate distinct gut microbiota composition in patients with FHA compared with healthy individuals. Importantly, HRT prompts a transition toward a more beneficial gut microbiota profile and reduced inflammation. This study validates the concept of FHA as a multifaceted disorder interlinked with dysbiosis, particularly involving the gut-brain axis.


Subject(s)
Gastrointestinal Microbiome , Humans , Female , Amenorrhea , Dysbiosis/metabolism , RNA, Ribosomal, 16S/genetics , Estrogens/pharmacology
2.
Liver Int ; 43(2): 370-380, 2023 02.
Article in English | MEDLINE | ID: mdl-36287108

ABSTRACT

BACKGROUND AND AIMS: Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut-liver axis and systemic inflammation. METHODS: Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota. RESULTS: PBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p = .01). Factors associated with LEAD at univariate analysis were VCAM-1 (p = .002), ICAM-1 (p = .003), and TNF-alpha (p = .04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0-1.1; p = .04) and TNF-alpha (OR 1.12, 95% CI 0.99-1.26; p = .04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR = 0.0008), Bifidobacterium (FDR = 0.001) and Oscillospira (FDR = 0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women. CONCLUSIONS: LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut-liver axis.


Subject(s)
Atherosclerosis , Hypercholesterolemia , Liver Cirrhosis, Biliary , Non-alcoholic Fatty Liver Disease , Humans , Female , Liver Cirrhosis, Biliary/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Tumor Necrosis Factor-alpha , Hypercholesterolemia/complications , Prevalence , Vascular Cell Adhesion Molecule-1 , Atherosclerosis/epidemiology , Atherosclerosis/complications , Lower Extremity
3.
Parasite Immunol ; 45(4): e12949, 2023 04.
Article in English | MEDLINE | ID: mdl-36063358

ABSTRACT

Humans have co-existed with parasites for virtually the entirety of our existence as a species. Today, nearly one third of the human population is infected with at least one helminthic species, most of which reside in the intestinal tract, where they have co-evolved alongside the human gut microbiota (GM). Appreciation for the interconnected relationship between helminths and GM has increased in recent years. Here, we review the evidence of how helminths and GM can influence various aspects of childhood development and the onset of paediatric diseases. We discuss the emerging evidence of how many of the changes that parasitic worms inflict on their host is enacted through gut microbes. In this light, we argue that helminth-induced microbiota modifications are of great importance in both facing the global challenge of overcoming parasitic infections, and in replicating helminthic protective effects against inflammatory diseases. We propose that deepening our knowledge of helminth-microbiota interactions will uncover novel, safer and more effective therapeutic strategies in combatting an array of childhood disorders.


Subject(s)
Gastrointestinal Microbiome , Helminths , Microbiota , Animals , Child , Humans
4.
Int J Mol Sci ; 24(7)2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37047594

ABSTRACT

Gut microbiota (GM) modulation can be investigated as possible solution to enhance recovery after COVID-19. An open-label, single-center, single-arm, pilot, interventional study was performed by enrolling twenty patients recently recovered from COVID-19 to investigate the role of a mixed probiotic, containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus, on gastrointestinal symptoms, local and systemic inflammation, intestinal barrier integrity and GM profile. Gastrointestinal Symptom Rating Scale, cytokines, inflammatory, gut permeability, and integrity markers were evaluated before (T0) and after 8 weeks (T1) of probiotic supplementation. GM profiling was based on 16S-rRNA targeted-metagenomics and QIIME 2.0, LEfSe and PICRUSt computational algorithms. Multiple machine learning (ML) models were trained to classify GM at T0 and T1. A statistically significant reduction of IL-6 (p < 0.001), TNF-α (p < 0.001) and IL-12RA (p < 0.02), citrulline (p value < 0.001) was reported at T1. GM global distribution and microbial biomarkers strictly reflected probiotic composition, with a general increase in Bifidobacteria at T1. Twelve unique KEGG orthologs were associated only to T0, including tetracycline resistance cassettes. ML classified the GM at T1 with 100% score at phylum level. Bifidobacteriaceae and Bifidobacterium spp. inversely correlated to reduction of citrulline and inflammatory cytokines. Probiotic supplementation during post-COVID-19 may trigger anti-inflammatory effects though Bifidobacteria and related-metabolism enhancement.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Probiotics , Humans , Gastrointestinal Microbiome/genetics , Citrulline , Probiotics/therapeutic use , Probiotics/pharmacology , Cytokines , Bifidobacterium , Machine Learning
5.
Pediatr Dermatol ; 39(5): 832-833, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35689474

ABSTRACT

Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional liposomal amphotericin B.


Subject(s)
Antiprotozoal Agents , Ear Auricle , Leishmaniasis, Cutaneous , Amphotericin B/therapeutic use , Antiprotozoal Agents/therapeutic use , Child , Family , Humans , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/drug therapy
6.
Int J Mol Sci ; 23(23)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36498975

ABSTRACT

Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet ß-cells, resulting in a marked loss of ß-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research.


Subject(s)
Diabetes Mellitus, Type 1 , Gastrointestinal Microbiome , Islets of Langerhans , Microbiota , Humans , Gastrointestinal Microbiome/physiology , Diabetes Mellitus, Type 1/genetics , Dysbiosis
7.
Int J Mol Sci ; 23(24)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36555624

ABSTRACT

Type 1 diabetes (T1D) is a chronic autoimmune metabolic disorder with onset in pediatric/adolescent age, characterized by insufficient insulin production, due to a progressive destruction of pancreatic ß-cells. Evidence on the correlation between the human gut microbiota (GM) composition and T1D insurgence has been recently reported. In particular, 16S rRNA-based metagenomics has been intensively employed in the last decade in a number of investigations focused on GM representation in relation to a pre-disease state or to a response to clinical treatments. On the other hand, few works have been published using alternative functional omics, which is more suitable to provide a different interpretation of such a relationship. In this work, we pursued a comprehensive metaproteomic investigation on T1D children compared with a group of siblings (SIBL) and a reference control group (CTRL) composed of aged matched healthy subjects, with the aim of finding features in the T1D patients' GM to be related with the onset of the disease. Modulated metaproteins were found either by comparing T1D with CTRL and SIBL or by stratifying T1D by insulin need (IN), as a proxy of ß-cells damage, showing some functional and taxonomic traits of the GM, possibly related to the disease onset at different stages of severity.


Subject(s)
Diabetes Mellitus, Type 1 , Gastrointestinal Microbiome , Insulin-Secreting Cells , Adolescent , Humans , Child , Aged , Gastrointestinal Microbiome/physiology , RNA, Ribosomal, 16S/genetics , Insulin, Regular, Human , Insulin
8.
Int J Mol Sci ; 23(22)2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36430609

ABSTRACT

Goat cheese is an important element of the Mediterranean diet, appreciated for its health-promoting features and unique taste. A pivotal role in the development of these characteristics is attributed to the microbiota and its continuous remodeling over space and time. Nevertheless, no thorough study of the cheese-associated microbiota using two metaomics approaches has previously been conducted. Here, we employed 16S rRNA gene sequencing and metaproteomics to explore the microbiota of a typical raw goat milk cheese at various ripening timepoints and depths of the cheese wheel. The 16S rRNA gene-sequencing and metaproteomics results described a stable microbiota ecology across the selected ripening timepoints, providing evidence for the microbiologically driven fermentation of goat milk products. The important features of the microbiota harbored on the surface and in the core of the cheese mass were highlighted in both compositional and functional terms. We observed the rind microbiota struggling to maintain the biosafety of the cheese through competition mechanisms and/or by preventing the colonization of the cheese by pathobionts of animal or environmental origin. The core microbiota was focused on other biochemical processes, supporting its role in the development of both the health benefits and the pleasant gustatory nuances of goat cheese.


Subject(s)
Cheese , Microbiota , One Health , Animals , Cheese/analysis , Goats/genetics , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Microbiota/genetics
9.
Int J Mol Sci ; 23(18)2022 Sep 06.
Article in English | MEDLINE | ID: mdl-36142163

ABSTRACT

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and 1H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.


Subject(s)
Diabetes Mellitus, Type 1 , Gastrointestinal Microbiome , Biomarkers/metabolism , Clostridiales/metabolism , Humans , Hydrogen-Ion Concentration , Isobutyrates , Malonates , Purines , Pyrimidines , RNA, Ribosomal, 16S/genetics
10.
Liver Int ; 41(6): 1320-1334, 2021 06.
Article in English | MEDLINE | ID: mdl-33713524

ABSTRACT

BACKGROUND & AIM: Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut-liver-muscle axis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients. METHODS: Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantification of muscle mass and strength were compared with age- and sex-matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed. RESULTS: The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function (Methanobrevibacter, Prevotella and Akkermansia), and was enriched in Eggerthella, a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro-inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chain amino acid metabolism were up-regulated, in addition to ethanol, trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred on Klebsiella/ethanol/FGF21/Eggerthella/Prevotella. CONCLUSIONS: Alterations in the gut-liver-muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network.


Subject(s)
Frailty , Gastrointestinal Microbiome , Sarcopenia , Humans , Liver Cirrhosis/complications
11.
J Inherit Metab Dis ; 44(3): 705-717, 2021 05.
Article in English | MEDLINE | ID: mdl-33325062

ABSTRACT

Pompe disease (PD) is caused by deficiency of the enzyme acid α-glucosidase resulting in glycogen accumulation in lysosomes. Clinical symptoms include skeletal myopathy, respiratory failure, and cardiac hypertrophy. We studied plasma proteomic and lipidomic profiles in 12 PD patients compared to age-matched controls. The proteomic profiles were analyzed by nLC-MS/MS SWATH method. Wide-targeted lipidomic analysis was performed by LC-IMS/MS, allowing to quantify >1100 lipid species, spanning 13 classes. Significant differences were found for 16 proteins, with four showing the most relevant changes (GPLD1, PON1, LDHB, PKM). Lipidomic analysis showed elevated levels of three phosphatidylcholines and of the free fatty acid 22:4, and reduced levels of six lysophosphatidylcholines. Up-regulated glycolytic enzymes (LDHB and PKM) are involved in autophagy and glycogen metabolism, while down-regulated PON1 and GPLD1 combined with lipidomic data indicate an abnormal phospholipid metabolism. Reduced GPLD1 and dysregulation of lipids with acyl-chains characteristic of GPI-anchor structure suggest the potential involvement of GPI-anchor system in PD. Results of proteomic analysis displayed the involvement of multiple cellular functions affecting inflammatory, immune and antioxidant responses, autophagy, Ca2+ -homeostasis, and cell adhesion. The combined multi-omic approach revealed new biosignatures in PD, providing novel insights in disease pathophysiology with potential future clinical application.


Subject(s)
Autophagy/physiology , Glycogen Storage Disease Type II/metabolism , Lipidomics/methods , Proteomics/methods , Adult , Aryldialkylphosphatase/metabolism , Child , Child, Preschool , Chromatography, Liquid , Female , Humans , Infant , Lactate Dehydrogenases/metabolism , Lipid Metabolism , Lysosomes/metabolism , Male , Phospholipids/metabolism , Tandem Mass Spectrometry
12.
Int J Mol Sci ; 22(4)2021 Feb 21.
Article in English | MEDLINE | ID: mdl-33669932

ABSTRACT

Background: Strongyloidiasis is a neglected tropical disease caused by the intestinal nematode Strongyloides stercoralis and characterized by gastrointestinal and pulmonary involvement. We report a pediatric case of strongyloidiasis to underline the response of the host microbiota to the perturbation induced by the nematode. Methods: We performed a 16S rRNA-metagenomic analysis of the gut microbiota of a 7-year-old female during and after S. stercolaris infection, investigating three time-point of stool samples' ecology: T0- during parasite infection, T1- a month after parasite infection, and T2- two months after parasite infection. Targeted-metagenomics were used to investigate ecology and to predict the functional pathways of the gut microbiota. Results: an increase in the alpha-diversity indices in T0-T1 samples was observed compared to T2 and healthy controls (CTRLs). Beta-diversity analysis showed a shift in the relative abundance of specific gut bacterial species from T0 to T2 samples. Moreover, the functional prediction of the targeted-metagenomics profiles suggested an enrichment of microbial glycan and carbohydrate metabolisms in the T0 sample compared with CTRLs. Conclusions: The herein report reinforces the literature suggestion of a putative direct or immune-mediated ability of S. stercolaris to promote the increase in bacterial diversity.


Subject(s)
Gastrointestinal Microbiome , Strongyloides stercoralis/physiology , Strongyloidiasis/microbiology , Strongyloidiasis/parasitology , Animals , Biodiversity , Child , Cluster Analysis , Female , Humans , Phylogeny , Principal Component Analysis , Strongyloides stercoralis/genetics , Strongyloides stercoralis/isolation & purification , Strongyloidiasis/metabolism
13.
Int J Mol Sci ; 22(4)2021 Feb 06.
Article in English | MEDLINE | ID: mdl-33562104

ABSTRACT

Food allergy (FA) and, in particular, IgE-mediated cow's milk allergy is associated with compositional and functional changes of gut microbiota. In this study, we compared the gut microbiota of cow's milk allergic (CMA) infants with that of cow's milk sensitized (CMS) infants and Healthy controls. The effect of the intake of a mixture of Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 on gut microbiota modulation of CMA infants and probiotic persistence was also investigated. Gut microbiota of CMA infants resulted to be characterized by a dysbiotic status with a prevalence of some bacteria as Haemophilus, Klebsiella, Prevotella, Actinobacillus and Streptococcus. Among the three strains administered, B.longum subsp. infantis colonized the gastrointestinal tract and persisted in the gut microbiota of infants with CMA for 60 days. This colonization was associated with perturbations of the gut microbiota, specifically with the increase of Akkermansia and Ruminococcus. Multi-strain probiotic formulations can be studied for their persistence in the intestine by monitoring specific bacterial probes persistence and exploiting microbiota profiling modulation before the evaluation of their therapeutic effects.


Subject(s)
Bifidobacterium breve/metabolism , Bifidobacterium longum subspecies infantis/metabolism , Bifidobacterium/metabolism , Gastrointestinal Microbiome/physiology , Milk Hypersensitivity/therapy , Probiotics/therapeutic use , Animals , Breast Feeding , Child, Preschool , Dysbiosis/microbiology , Female , Humans , Immunoglobulin E/immunology , Infant , Male , Milk/immunology , Milk Hypersensitivity/microbiology
14.
J Transl Med ; 18(1): 49, 2020 02 03.
Article in English | MEDLINE | ID: mdl-32014010

ABSTRACT

BACKGROUND: Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy. METHODS: The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses. RESULTS: Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects. CONCLUSIONS: Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Gastrointestinal Microbiome , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Metabolomics
15.
Hepatology ; 69(1): 107-120, 2019 01.
Article in English | MEDLINE | ID: mdl-29665135

ABSTRACT

The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Conclusion: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis.


Subject(s)
Carcinoma, Hepatocellular/congenital , Carcinoma, Hepatocellular/microbiology , Gastrointestinal Microbiome , Inflammation/complications , Liver Cirrhosis/complications , Liver Neoplasms/complications , Liver Neoplasms/microbiology , Non-alcoholic Fatty Liver Disease/complications , Aged , Female , Humans , Male , Middle Aged
16.
Int J Mol Sci ; 21(10)2020 May 23.
Article in English | MEDLINE | ID: mdl-32456257

ABSTRACT

The human gut contains trillions of microbes that play a central role in host biology, including the provision of key nutrients from the diet. Food is a major source of precursors for metabolite production; in fact, diet modulates the gut microbiota (GM) as the nutrients, derived from dietary intake, reach the GM, affecting both the ecosystem and microbial metabolic profile. GM metabolic ability has an impact on human nutritional status from childhood. However, there is a wide variability of dietary patterns that exist among individuals. The study of interactions with the host via GM metabolic pathways is an interesting field of research in medicine, as microbiota members produce myriads of molecules with many bioactive properties. Indeed, much evidence has demonstrated the importance of metabolites produced by the bacterial metabolism from foods at the gut level that dynamically participate in various biochemical mechanisms of a cell as a reaction to environmental stimuli. Hence, the GM modulate homeostasis at the gut level, and the alteration in their composition can concur in disease onset or progression, including immunological, inflammatory, and metabolic disorders, as well as cancer. Understanding the gut microbe-nutrient interactions will increase our knowledge of how diet affects host health and disease, thus enabling personalized therapeutics and nutrition.


Subject(s)
Diet , Gastrointestinal Microbiome , Diet Therapy/methods , Host-Pathogen Interactions , Humans , Prebiotics/administration & dosage , Probiotics/therapeutic use
17.
Int J Mol Sci ; 21(17)2020 Aug 30.
Article in English | MEDLINE | ID: mdl-32872562

ABSTRACT

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.


Subject(s)
Autism Spectrum Disorder/diagnosis , Biomarkers/analysis , Metabolome , Precision Medicine , Proteome/analysis , Autism Spectrum Disorder/metabolism , Humans , Phenotype
18.
Int J Mol Sci ; 21(22)2020 Nov 19.
Article in English | MEDLINE | ID: mdl-33227982

ABSTRACT

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gastrointestinal Microbiome/immunology , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Lung Neoplasms/genetics , Metabolome/immunology , Akkermansia/classification , Akkermansia/genetics , Akkermansia/isolation & purification , Alcohols/metabolism , Aldehydes/metabolism , Antineoplastic Agents, Immunological/therapeutic use , Bacteroides/classification , Bacteroides/genetics , Bacteroides/isolation & purification , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/microbiology , Clostridiaceae/classification , Clostridiaceae/genetics , Clostridiaceae/isolation & purification , Databases, Genetic , Disease Progression , Drug Monitoring/methods , Fatty Acids, Volatile/metabolism , Gastrointestinal Microbiome/genetics , Humans , Immunotherapy/methods , Indoles/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/microbiology , Metabolome/genetics , Metagenomics/methods , Peptostreptococcus/classification , Peptostreptococcus/genetics , Peptostreptococcus/isolation & purification , Precision Medicine/methods , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , RNA, Ribosomal, 16S/genetics , Signal Transduction
19.
Gut ; 68(12): 2111-2121, 2019 12.
Article in English | MEDLINE | ID: mdl-31563878

ABSTRACT

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.


Subject(s)
Clostridioides difficile/isolation & purification , Clostridium Infections/therapy , Consensus , Fecal Microbiota Transplantation/methods , Gastrointestinal Microbiome , Clostridium Infections/microbiology , Donor Selection , Humans , Specimen Handling/methods
20.
Metabolomics ; 15(2): 20, 2019 02 02.
Article in English | MEDLINE | ID: mdl-30830433

ABSTRACT

OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates. STUDY DESIGN: Metabolomic study of prospectively collected tracheal aspirate (TA) samples from preterm neonates admitted in 2 neonatal intensive care units measured by a mass spectroscopy-based assay and analysed using partial least squares-discriminant analysis. RESULTS: We evaluated 160 TA samples from 68 neonates, 44 with BPD and 24 without BPD in the first week of life. A cluster of 53 metabolites was identified as characteristic of BPD, with 18 select metabolites being highly significant in the separation of BPD versus No BPD. To control for the gestational age (GA) differences, we did a sub-group analyses, and noted that the amino acids histidine, glutamic acid, citrulline, glycine and isoleucine levels were higher in neonates with BPD. In addition, acylcarnitines C16-OH and C18:1-OH were also higher in neonates who developed BPD, but especially in the most preterm infants (neonates with GA < 27 weeks). CONCLUSION: Metabolomics is a promising approach to identify novel specific biomarkers for BPD.


Subject(s)
Biomarkers/metabolism , Bronchopulmonary Dysplasia/metabolism , Metabolomics/methods , Biomarkers/analysis , Cluster Analysis , Discriminant Analysis , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature/metabolism , Male , Mass Spectrometry/methods , Prospective Studies
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