Publications by authors named "Danilo Ercolini"

136 Publications

Outlook on next-generation probiotics from the human gut.

Cell Mol Life Sci 2022 Jan 19;79(2):76. Epub 2022 Jan 19.

Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy.

Probiotics currently available on the market generally belong to a narrow range of microbial species. However, recent studies about the importance of the gut microbial commensals on human health highlighted that the gut microbiome is an unexplored reservoir of potentially beneficial microbes. For this reason, academic and industrial research is focused on identifying and testing novel microbial strains of gut origin for the development of next-generation probiotics. Although several of these are promising for the prevention and treatment of many chronic diseases, studies on human subjects are still scarce and approval from regulatory agencies is, therefore, rare. In addition, some issues need to be overcome before implementing their wide application on the market, such as the best methods for cultivation and storage of these oxygen-sensitive taxa. This review summarizes the most recent evidence related to NGPs and provides an outlook to the main issues that still limit their wide employment.
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http://dx.doi.org/10.1007/s00018-021-04080-6DOI Listing
January 2022

Next-Generation Food Research: Use of Meta-Omic Approaches for Characterizing Microbial Communities Along the Food Chain.

Annu Rev Food Sci Technol 2021 Oct 22. Epub 2021 Oct 22.

Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland; email:

Microorganisms exist along the food chain and impact the quality and safety of foods in both positive and negative ways. Identifying and understanding the behavior of these microbial communities enable the implementation of preventative or corrective measures in public health and food industry settings. Current culture-dependent microbial analyses are time-consuming and target only specific subsets of microbes. However, the greater use of culture-independent meta-omic approaches has the potential to facilitate a thorough characterization of the microbial communities along the food chain. Indeed, these methods have shown potential in contributing to outbreak investigation, ensuring food authenticity, assessing the spread of antimicrobial resistance, tracking microbial dynamics during fermentation and processing, and uncovering the factors along the food chain that impact food quality and safety. This review examines the community-based approaches, and particularly the application of sequencing-based meta-omics strategies, for characterizing microbial communities along the food chain. Expected final online publication date for the , Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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http://dx.doi.org/10.1146/annurev-food-052720-010751DOI Listing
October 2021

Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance.

Nat Commun 2021 10 13;12(1):5958. Epub 2021 Oct 13.

Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy.

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.
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http://dx.doi.org/10.1038/s41467-021-26266-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514477PMC
October 2021

Identification and Characterization of Human Observational Studies in Nutritional Epidemiology on Gut Microbiomics for Joint Data Analysis.

Nutrients 2021 Sep 21;13(9). Epub 2021 Sep 21.

INSERM UMR 1073 "Nutrition, Inflammation and Gut-Brain Axis Dysfunctions", UNIROUEN, Normandie University, 76000 Rouen, France.

In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease.
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http://dx.doi.org/10.3390/nu13093292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466729PMC
September 2021

Stool microRNA profiles reflect different dietary and gut microbiome patterns in healthy individuals.

Gut 2021 Jul 27. Epub 2021 Jul 27.

Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Torino, Italy

Objectives: MicroRNA (miRNA) profiles have been evaluated in several biospecimens in relation to common diseases for which diet may have a considerable impact. We aimed at characterising how specific diets are associated with the miRNome in stool of vegans, vegetarians and omnivores and how this is reflected in the gut microbial composition, as this is still poorly explored.

Design: We performed small RNA and shotgun metagenomic sequencing in faecal samples and dietary recording from 120 healthy volunteers, equally distributed for the different diets and matched for sex and age.

Results: We found 49 miRNAs differentially expressed among vegans, vegetarians and omnivores (adj. p <0.05) and confirmed trends of expression levels of such miRNAs in vegans and vegetarians compared with an independent cohort of 45 omnivores. Two miRNAs related to lipid metabolism, miR-636 and miR-4739, were inversely correlated to the non-omnivorous diet duration, independently of subject age. Seventeen miRNAs correlated (|rho|>0.22, adj. p <0.05) with the estimated intake of nutrients, particularly animal proteins, phosphorus and, interestingly, lipids. In omnivores, higher and and lower abundances than in vegans and vegetarians were observed. Lipid metabolism-related miR-425-3p and miR-638 expression levels were associated with increased abundances of microbial species, such as sp. CAG 182 and specific of different diets. An integrated analysis identified 25 miRNAs, 25 taxa and 7 dietary nutrients that clearly discriminated (area under the receiver operating characteristic curve=0.89) the three diets.

Conclusion: Stool miRNA profiles are associated with specific diets and support the role of lipids as a driver of epigenetic changes and host-microbial molecular interactions in the gut.
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http://dx.doi.org/10.1136/gutjnl-2021-325168DOI Listing
July 2021

The Vaginal Microbiome: A Long Urogenital Colonization Throughout Woman Life.

Front Cell Infect Microbiol 2021 6;11:686167. Epub 2021 Jul 6.

Dipartimento di Medicina Clinica e Chirurgia, Università Federico II di Napoli, Naples, Italy.

Vaginal microbial niche is a dynamic ecosystem, composed by more than 200 bacterial species which are influenced by genes, ethnic background and environmental-behavioral factors. Several lines of evidence have well documented that vaginal microbiome constantly changes over the course of woman's life, so to exert an important impact on woman quality of life, from newborn to post-menopausal ages. This review aims at analyzing the role of vaginal microbiome in the maintenance of woman's homeostasis and at tracking critical changes that commonly occur across woman's lifetime. The role of hormone replacement therapy in the modulation of vaginal microbiome composition and in the improvement of vaginal wellness in postmenopausal women with decreasing levels of circulating estrogen is discussed.
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http://dx.doi.org/10.3389/fcimb.2021.686167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290858PMC
July 2021

Prevotella diversity, niches and interactions with the human host.

Nat Rev Microbiol 2021 09 28;19(9):585-599. Epub 2021 May 28.

Department CIBIO, University of Trento, Trento, Italy.

The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host-Prevotella symbiotic relationship in the context of maintaining human health.
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http://dx.doi.org/10.1038/s41579-021-00559-yDOI Listing
September 2021

A global metagenomic map of urban microbiomes and antimicrobial resistance.

Cell 2021 06 26;184(13):3376-3393.e17. Epub 2021 May 26.

Weill Cornell Medicine, New York, NY, USA; The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, New York, NY, USA.

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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http://dx.doi.org/10.1016/j.cell.2021.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238498PMC
June 2021

Mediterranean diet consumption affects the endocannabinoid system in overweight and obese subjects: possible links with gut microbiome, insulin resistance and inflammation.

Eur J Nutr 2021 Oct 24;60(7):3703-3716. Epub 2021 Mar 24.

Department of Agricultural Sciences, University of Naples Federico II, Parco Gussone Ed. 84, 80055, Portici, NA), Italy.

Purpose: To investigate whether a Mediterranean diet (MD) affected the plasma concentrations of endocannabinoids (ECs), N-acylethanolamines (NAEs) and their specific ratios in subjects with lifestyle risk factors for metabolic diseases. To identify the relationship between circulating levels of these compounds and gut microbiome, insulin resistance and systemic inflammation.

Methods: A parallel 8-week randomised controlled trial was performed involving 82 overweight and obese subjects aged (mean ± SEM) 43 ± 1.4 years with a BMI of 31.1 ± 0.5 kg/m, habitual Western diet (CT) and sedentary lifestyle. Subjects were randomised to consume an MD tailored to their habitual energy and macronutrient intake (n = 43) or to maintain their habitual diet (n = 39). Endocannabinoids and endocannabinoid-like molecules, metabolic and inflammatory markers and gut microbiome were monitored over the study period.

Results: The MD intervention lowered plasma arachidonoylethanolamide (AEA, p = 0.02), increased plasma oleoylethanolamide/palmitoylethanolamide (OEA/PEA, p = 0.009) and OEA/AEA (p = 0.006) and increased faecal Akkermansia muciniphila (p = 0.026) independent of body weight changes. OEA/PEA positively correlated with abundance of key microbial players in diet-gut-health interplay and MD adherence. Following an MD, individuals with low-plasma OEA/PEA at baseline decreased homeostatic model assessment of insulin resistance index (p = 0.01), while individuals with high-plasma OEA/PEA decreased serum high-sensitive C-reactive protein (p = 0.02).

Conclusions: We demonstrated that a switch from a CT to an isocaloric MD affects the endocannabinoid system and increases A. muciniphila abundance in the gut independently of body weight changes. Endocannabinoid tone and microbiome functionality at baseline drives an individualised response to an MD in ameliorating insulin sensitivity and inflammation. Clinical Trial Registry number and website NCT03071718; www.clinicaltrials.gov.
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http://dx.doi.org/10.1007/s00394-021-02538-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437855PMC
October 2021

Microbiota thrombus colonization may influence athero-thrombosis in hyperglycemic patients with ST segment elevation myocardialinfarction (STEMI). Marianella study.

Diabetes Res Clin Pract 2021 Mar 14;173:108670. Epub 2021 Jan 14.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli" Italy, Italy.

Objectives: We examined the association of the coronary thrombus microbiota and relative metabolites with major adverse cardiovascular events (MACE) in hyperglycemic patients with ST segment elevation myocardial infarction (STEMI).

Background: Hyperglycemia during STEMI may affect both development and progression of coronary thrombus via gut and thrombus microbiota modifications.

Methods: We undertook an observational cohort study of 146 first STEMI patients treated with primary percutaneous coronary intervention (PPCI) and thrombus-aspiration (TA). Patients were clustered, based on admission blood glucose levels, in hyperglycemic (≥140 mg/dl) and normoglycemic (<140 mg/dl). We analyzed gut and thrombus microbiota in all patients. Moreover, we assessed TMAO, CD40L and von Willebrand Factor (vWF) in coronary thrombi. Cox regressions were used for the association between Prevotellaspp. and TMAO terziles and MACE. MACE endpoint at 1 year included death, re-infarction, unstable angina.

Results: In fecal and thrombus samples, we observed a significantly different prevalence of both Prevotellaspp. and Alistipesspp. between patients with hyperglycemia (n = 56) and those with normal glucose levels (n = 90). The abundance of Prevotella increased in hyperglycemic vs normoglycemic patients whereas the contrary was observed for Alistipes. Interestingly, in coronary thrombus, the content of Prevotella was associated with admission blood glucose levels (p < 0.01), thrombus dimensions (p < 0.01), TMAO, CDL40 (p < 0.01) and vWF (p < 0.01) coronary thrombus contents. Multivariate Cox-analysis disclosed a reduced survival in patients with high levels of Prevotella and TMAO in coronary thrombus as compared to patients with low levels of Prevotella and TMAO, after 1-year follow up.

Conclusions: Hyperglycemia during STEMI may increase coronary thrombus burden via gut and thrombus microbiota dysbiosis characterized by an increase of Prevotella and TMAO content in thrombi.

Clinical Trial Registration: NCT03439592. September 30, 2016. Ethic Committee Vanvitelli University: 268/2016.
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http://dx.doi.org/10.1016/j.diabres.2021.108670DOI Listing
March 2021

The Interrelationship Between Microbiota and Peptides During Ripening as a Driver for Parmigiano Reggiano Cheese Quality.

Front Microbiol 2020 2;11:581658. Epub 2020 Oct 2.

Department of Food and Drug, University of Parma, Parma, Italy.

Cheese microbiota contribute significantly to the final characteristics of cheeses due to the growth and interaction between cheese microorganisms during processing and ripening. For raw milk cheeses, such as Parmigiano Reggiano (PR), the microbiota derive from the raw milk itself, the dairy environment, and the starter. The process of cheese making and time of ripening shape this complex ecosystem through the selection of different species and biotypes that will drive the quality of the final product by performing functions of their metabolism such as proteolysis. The diversity in the final peptide and amino acid composition of the cheese is thus mostly linked to the diversity of this microbiota. The purpose of this study was to get more insight into the factors affecting PR cheese diversity and, more specifically, to evaluate whether the composition of the bacterial community of cheeses along with the specific peptide composition are more affected by the ripening times or by the cheese making process. To this end, the microbiota and the peptide fractions of 69 cheese samples (from curd to cheese ripened 24 months) were analyzed during 6 complete PR production cycles, which were performed in six different dairies located in the PR production area. The relation among microbial dynamics, peptide evolution, and ripening times were investigated in this unique and tightly controlled production and sampling set up. The study of microbial and peptide moieties in products from different dairies - from curd to at least 12 months, the earliest time from which the cheese can be sold, and up to a maximum of 24 months of ripening - highlighted the presence of differences between samples coming from different dairies, probably due to small differences in the cheese making process. Besides these differences, however, ripening time had by far the greatest impact on microbial dynamics and, consequently, on peptide composition.
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http://dx.doi.org/10.3389/fmicb.2020.581658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561718PMC
October 2020

Newly Explored Faecalibacterium Diversity Is Connected to Age, Lifestyle, Geography, and Disease.

Curr Biol 2020 12 15;30(24):4932-4943.e4. Epub 2020 Oct 15.

Department of Agricultural Sciences, University of Naples Federico II, Portici 80055, Italy; Task Force on Microbiome Studies, University of Naples Federico II, Naples 80100, Italy. Electronic address:

Faecalibacterium is prevalent in the human gut and a promising microbe for the development of next-generation probiotics (NGPs) or biotherapeutics. Analyzing reference Faecalibacterium genomes and almost 3,000 Faecalibacterium-like metagenome-assembled genomes (MAGs) reconstructed from 7,907 human and 203 non-human primate gut metagenomes, we identified the presence of 22 different Faecalibacterium-like species-level genome bins (SGBs), some further divided in different strains according to the subject geographical origin. Twelve SGBs are globally spread in the human gut and show different genomic potential in the utilization of complex polysaccharides, suggesting that higher SGB diversity may be related with increased utilization of plant-based foods. Moreover, up to 11 different species may co-occur in the same subject, with lower diversity in Western populations, as well as intestinal inflammatory states and obesity. The newly explored Faecalibacterium diversity will be able to support the choice of strains suitable as NGPs, guided by the consideration of the differences existing in their functional potential.
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http://dx.doi.org/10.1016/j.cub.2020.09.063DOI Listing
December 2020

Distribution of Antibiotic Resistance Genes in the Saliva of Healthy Omnivores, Ovo-Lacto-Vegetarians, and Vegans.

Genes (Basel) 2020 09 18;11(9). Epub 2020 Sep 18.

Department of Agricultural, Food and Environmental Sciences (D3A), Università Politecnica delle Marche, 60131 Ancona, Italy.

Food consumption allows the entrance of bacteria and their antibiotic resistance (AR) genes into the human oral cavity. To date, very few studies have examined the influence of diet on the composition of the salivary microbiota, and even fewer investigations have specifically aimed to assess the impact of different long-term diets on the salivary resistome. In this study, the saliva of 144 healthy omnivores, ovo-lacto-vegetarians, and vegans were screened by nested PCR for the occurrence of 12 genes conferring resistance to tetracyclines, macrolide-lincosamide-streptogramin B, vancomycin, and β-lactams. The (W), (M), and (B) genes occurred with the highest frequencies. Overall, no effect of diet on AR gene distribution was seen. Some differences emerged at the recruiting site level, such as the higher frequency of (C) in the saliva of the ovo-lacto-vegetarians and omnivores from Bologna and Turin, respectively, and the higher occurrence of (K) in the saliva of the omnivores from Bologna. A correlation of the intake of milk and cheese with the abundance of (K) and (C) genes was seen. Finally, when the occurrence of the 12 AR genes was evaluated along with geographical location, age, and sex as sources of variability, high similarity among the 144 volunteers was seen.
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http://dx.doi.org/10.3390/genes11091088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564780PMC
September 2020

Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: Can SCFAs play a role?

Clin Nutr 2021 02 3;40(2):428-437. Epub 2020 Jun 3.

Dept. of Clinical Medicine and Surgery, "Federico II" University of Naples, Italy; Task Force on Microbiome Studies, University of Naples "Federico II", Naples, Italy. Electronic address:

Background & Aims: Postprandial metabolic abnormalities are considered important and independent risk factors for cardiovascular diseases. However, the effects of the Mediterranean diet on postprandial metabolism and the mechanism underpinning the effects on clinical variables have not been exhaustively explored. Therefore, the aims of the present study were to evaluate the acute and medium-term effects (8 weeks) on postprandial glucose and lipid metabolism of a diet resembling a typical Mediterranean diet (Med-D) compared to a western-type diet (Control-D), and the mechanisms underlying those effects.

Methods: Twenty-nine overweight/obese individuals of both genders, aged 20-60 years, were enrolled and randomly assigned to two isoenergetic dietary interventions: 1) a Med-D (n = 16), and 2) a Control-D (n = 13). Adherence to the dietary interventions was assessed by a 7-day food record. A meal test resembling the assigned diet was performed at baseline and after 8 weeks of intervention. Blood samples at fasting and over 4-h after the meal were collected to assess metabolic parameters and short chain fatty acid (SCFA) levels. Fecal samples were also collected to evaluate the microbiota composition.

Results: Glucose and insulin responses were significantly reduced at baseline after the Med test meal compared to the Control meal (p < 0.05) and this effect was strengthened after 8 weeks of intervention with the Mediterranean diet (p < 0.05); together with an improvement in OGIS. At the end of the intervention, postprandial plasma butyric acid incremental area under the curve (IAUC) was significantly increased in the Med-D group (p = 0.019) and correlated inversely with plasma insulin IAUC and directly with oral glucose insulin sensitivity (OGIS) (r: -0.411, p = 0.046 and r: 0.397, p = 0.050 respectively). These metabolic changes were accompanied by significant changes in gut microbiota, such as an increase in the relative abundance of Intestinimonas butyriciproducens and Akkermansia muciniphila (p < 0.05) in the Med-D compared to Control-D group.

Conclusions: Our study provides strong evidence that a diet resembling the traditional Med-D improves postprandial glucose metabolism and insulin sensitivity. Furthermore, the study highlights a possible involvement of gut microbiota metabolites - such as butyric acid, and of dietary fiber as a precursor - in improving glucose metabolism and insulin sensitivity.
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http://dx.doi.org/10.1016/j.clnu.2020.05.025DOI Listing
February 2021

The food-gut axis: lactic acid bacteria and their link to food, the gut microbiome and human health.

FEMS Microbiol Rev 2020 07;44(4):454-489

Department of Agricultural Sciences, University of Naples Federico II, via Università, 100, 80055, Portici (NA) Italy.

Lactic acid bacteria (LAB) are present in foods, the environment and the animal gut, although fermented foods (FFs) are recognized as the primary niche of LAB activity. Several LAB strains have been studied for their health-promoting properties and are employed as probiotics. FFs are recognized for their potential beneficial effects, which we review in this article. They are also an important source of LAB, which are ingested daily upon FF consumption. In this review, we describe the diversity of LAB and their occurrence in food as well as the gut microbiome. We discuss the opportunities to study LAB diversity and functional properties by considering the availability of both genomic and metagenomic data in public repositories, as well as the different latest computational tools for data analysis. In addition, we discuss the role of LAB as potential probiotics by reporting the prevalence of key genomic features in public genomes and by surveying the outcomes of LAB use in clinical trials involving human subjects. Finally, we highlight the need for further studies aimed at improving our knowledge of the link between LAB-fermented foods and the human gut from the perspective of health promotion.
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http://dx.doi.org/10.1093/femsre/fuaa015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391071PMC
July 2020

Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome.

Nat Commun 2020 05 25;11(1):2610. Epub 2020 May 25.

Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy.

Lactic acid bacteria (LAB) are fundamental in the production of fermented foods and several strains are regarded as probiotics. Large quantities of live LAB are consumed within fermented foods, but it is not yet known to what extent the LAB we ingest become members of the gut microbiome. By analysis of 9445 metagenomes from human samples, we demonstrate that the prevalence and abundance of LAB species in stool samples is generally low and linked to age, lifestyle, and geography, with Streptococcus thermophilus and Lactococcus lactis being most prevalent. Moreover, we identify genome-based differences between food and gut microbes by considering 666 metagenome-assembled genomes (MAGs) newly reconstructed from fermented food microbiomes along with 154,723 human MAGs and 193,078 reference genomes. Our large-scale genome-wide analysis demonstrates that closely related LAB strains occur in both food and gut environments and provides unprecedented evidence that fermented foods can be indeed regarded as a possible source of LAB for the gut microbiome.
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http://dx.doi.org/10.1038/s41467-020-16438-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248083PMC
May 2020

A Mediterranean Diet Intervention Reduces the Levels of Salivary Periodontopathogenic Bacteria in Overweight and Obese Subjects.

Appl Environ Microbiol 2020 06 2;86(12). Epub 2020 Jun 2.

Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy

The human oral cavity is a complex ecosystem, and the alterations in salivary microbial communities are associated with both oral and nonoral diseases. The Mediterranean diet (MD) is a healthy dietary pattern useful for both prevention and treatment of several diseases. To further explore the effects of the MD on human health, in this study, we investigated the changes in the salivary microbial communities in overweight/obese subjects after an individually tailored MD-based nutritional intervention. Healthy overweight and obese subjects were randomized between two intervention groups. The MD group (Med-D group) increased their MD adherence during 8 weeks of intervention while the control diet (control-D) group did not change their dietary habits. The salivary microbiota was assessed at baseline and after 4 and 8 weeks of intervention. Despite no observed changes in the overall salivary microbiota composition, we found a significant decrease in the relative abundances of species-level operational taxonomic units annotated as , , and in the Med-D group compared to that in the control-D group after 8 weeks of intervention, which are known to be associated with periodontal disease. Such variations were significantly linked to dietary variables such as MD adherence rates and intakes of animal versus vegetable proteins. In addition, increased levels of were observed in the Med-D group, which has been reported as an antagonistic taxon inhibiting gene expression. Our findings suggest that an MD-based nutritional intervention may be implicated in reducing periodontal bacteria, and an MD may be a dietary strategy supportive of oral homeostasis. Changes in dietary behavior with increased adherence to a Mediterranean diet can determine a reduction of periodontopathogenic bacterial abundances in the saliva of overweight subjects with cardiometabolic risk due to an unhealthy lifestyle, without any change in individual energy intake, nutrient intake, and physical activity.
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http://dx.doi.org/10.1128/AEM.00777-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267188PMC
June 2020

One ring to rule them all: an ecosystem engineer fungus fosters plant and microbial diversity in a Mediterranean grassland.

New Phytol 2020 08 9;227(3):884-898. Epub 2020 May 9.

Dipartimento di Agraria, Università di Napoli Federico II, Via Università, 100, 80055, Portici, Naples, Italy.

Species coexistence in grasslands is regulated by several environmental factors and interactions with the soil microbial community. Here, the development of the Basidiomycetes fungus Agaricus arvensis, forming fairy rings, in a species-rich Mediterranean grassland, is described. Effects of the mycelial front on plants, fungi and bacteria were assessed by vegetation survey and next generation sequencing approaches. Our results showed a fungal-dependent shift in the community structure operated by a wave-like spread of fairy rings that decreased plant, fungal and bacterial diversity, indicating a detrimental effect of fairy rings on most species. The fairy rings induced successional processes in plants that enhanced the replacement of a community dominated by perennial plants with short-living and fast-growing plant species. In parallel, fungal and bacterial communities showed evident differences in species composition with several taxa associated within distinct sampling zone across the fairy rings. Notably, bacteria belonging to the Burkholderia genus and fungi of the genus Trichoderma increased in response to the advancing mycelium of A. arvensis. The profound changes in community composition and the overall increase in taxa diversity at ecosystemic scale suggest that fairy ring-forming fungi may act as ecosystem engineer species in Mediterranean grasslands.
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http://dx.doi.org/10.1111/nph.16583DOI Listing
August 2020

Diet influences the functions of the human intestinal microbiome.

Sci Rep 2020 03 6;10(1):4247. Epub 2020 Mar 6.

Department of Agricultural, Forest and Food Science, University of Turin, Grugliasco, Italy.

Gut microbes programme their metabolism to suit intestinal conditions and convert dietary components into a panel of small molecules that ultimately affect host physiology. To unveil what is behind the effects of key dietary components on microbial functions and the way they modulate host-microbe interaction, we used for the first time a multi-omic approach that goes behind the mere gut phylogenetic composition and provides an overall picture of the functional repertoire in 27 fecal samples from omnivorous, vegan and vegetarian volunteers. Based on our data, vegan and vegetarian diets were associated to the highest abundance of microbial genes/proteins responsible for cell motility, carbohydrate- and protein-hydrolyzing enzymes, transport systems and the synthesis of essential amino acids and vitamins. A positive correlation was observed when intake of fiber and the relative fecal abundance of flagellin were compared. Microbial cells and flagellin extracted from fecal samples of 61 healthy donors modulated the viability of the human (HT29) colon carcinoma cells and the host response through the stimulation of the expression of Toll-like receptor 5, lectin RegIIIα and three interleukins (IL-8, IL-22 and IL-23). Our findings concretize a further and relevant milestone on how the diet may prevent/mitigate disease risk.
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http://dx.doi.org/10.1038/s41598-020-61192-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060259PMC
March 2020

Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.

Gut 2020 07 19;69(7):1258-1268. Epub 2020 Feb 19.

Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy

Objectives: This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.

Design: Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.

Results: Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.

Conclusion: Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.
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http://dx.doi.org/10.1136/gutjnl-2019-320438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306983PMC
July 2020

The fate of cigarette butts in different environments: Decay rate, chemical changes and ecotoxicity revealed by a 5-years decomposition experiment.

Environ Pollut 2020 Jun 31;261:114108. Epub 2020 Jan 31.

DI4A, Department of Agri-Food, Environmental and Animal Sciences, University of Udine, via delle Scienze 206, 33100, Udine, Italy.

Cigarette butts (CBs) are the most common litter item on Earth but no long-term studies evaluate their fate and ecological effects. Here, the role of nitrogen (N) availability and microbiome composition on CBs decomposition were investigated by a 5-years experiment carried out without soil, in park grassland and sand dune. During decomposition, CBs chemical changes was assessed by both C CPMAS NMR and LC-MS, physical structure by scanning electron microscope and ecotoxicity by Aliivibrio fischeri and Raphidocelis subcapitata. Microbiota was investigated by high-throughput sequencing of bacterial and eukaryotic rRNA gene markers. CBs followed a three-step decomposition process: at the early stage (∼30 days) CBs lost ∼15.2% of their mass. During the subsequent two years CBs decomposed very slowly, taking thereafter different trajectories depending on N availability and microbiome composition. Without soil CBs showed minor chemical and morphological changes. Over grassland soil a consistent N transfer occurs that, after de-acetylation, promote CBs transformation into an amorphous material rich in aliphatic compounds. In sand dune we found a rich fungal microbiota able to decompose CBs, even before the occurrence of de-acetylation. CBs ecotoxicity was highest immediately after smoking. However, for R. subcapitata toxicity remained high after two and five years of decomposition.
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http://dx.doi.org/10.1016/j.envpol.2020.114108DOI Listing
June 2020

Attenuated Lactococcus lactis and Surface Bacteria as Tools for Conditioning the Microbiota and Driving the Ripening of Semisoft Caciotta Cheese.

Appl Environ Microbiol 2020 02 18;86(5). Epub 2020 Feb 18.

Faculty of Science and Technology, Free University of Bozen, Bolzano, Italy.

This study aimed at establishing the effects of attenuated starters and surface bacteria on various features of caciotta cheese. The cheese undergoes a ripening period during which the house microbiota contaminates the surface. Conventional cheese (the control cheese [CC]) is made using only primary starters. Primary starters and attenuated (i.e., unable to grow and synthesize lactic acid) () subsp. were used to produce caciotta cheese without (ATT cheese) or with an inoculum of surface bacteria: (i) () (LL cheese), (ii) (VC cheese), (iii) (SE cheese), (iv) (BX cheese), and (v) a mixture of all four (MIX cheese). Attenuated increased microbial diversity during cheese ripening. At the core, attenuated starter mainly increased indigenous lactococci and group bacteria. At the surface, the main effect was on Autochthonous strains took advantage of the attenuated starter, becoming dominant. Adjunct positively affected group bacteria on the LL cheese surface. Adjunct , , and did not become dominant. Surfaces of VC, SE, and BX cheeses mainly harbored Peptidase activities were higher in cheeses made with attenuated starter than in CC, which had the lowest concentration of free amino acids. Based on the enzymatic activities of adjunct , LL and MIX cheeses exhibited the highest glutamate dehydrogenase, cystathionine-γ-lyase, and esterase activities. As shown by multivariate statistical analyses, LL and MIX cheeses showed the highest similarity for microbiological and biochemical features. LL and MIX cheeses received the highest scores for overall sensory acceptability. This study provides in-depth knowledge of the effects of attenuated starters and surface bacterial strains on the microbiota and related metabolic activities during cheese ripening. The use of attenuated strongly impacted the microbiota assembly of caciotta cheese. This led to improved biochemical and sensory features compared to conventional cheese. Among surface bacterial strains, played a key role in the metabolic activities involved in cheese ripening. This resulted in an improvement of the sensory quality of caciotta cheese. The use of attenuated lactic acid bacteria and the surface adjunct could be a useful biotechnology to improve the flavor formation of caciotta cheese.
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http://dx.doi.org/10.1128/AEM.02165-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028956PMC
February 2020

The therapeutic efficacy of Bifidobacterium animalis subsp. lactis BB-12 in infant colic: A randomised, double blind, placebo-controlled trial.

Aliment Pharmacol Ther 2020 01 3;51(1):110-120. Epub 2019 Dec 3.

Department of Translational Medical Science, University of Naples Federico II, Naples, Italy.

Background: The pathogenesis of infant colic is poorly defined. Gut microbiota seems to be involved, supporting the potential therapeutic role of probiotics.

Aims: To assess the rate of infants with a reduction of ≥50% of mean daily crying duration after 28 days of intervention with the probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB-12). Secondary outcomes were daily number of crying episodes, sleeping time, number of bowel movements and stool consistency.

Methods: Randomized controlled trial (RCT) on otherwise healthy exclusively breastfed infants with infant colic randomly allocated to receive BB-12 (1 × 10  CFU/day) or placebo for 28 days. Gut microbiota structure and butyrate, beta-defensin-2 (HBD-2), cathelicidin (LL-37), secretory IgA (sIgA) and faecal calprotectin levels were assessed.

Results: Eighty infants were randomised, 40/group. The rate of infants with reduction of ≥50% of mean daily crying duration was higher in infants treated with BB-12, starting from the end of 2nd week. No infant relapsed when treatment was stopped. The mean number of crying episodes decreased in both groups, but with a higher effect in BB-12 group (-4.7 ± 3.4 vs -2.3 ± 2.2, P < 0.05). Mean daily stool frequency decreased in both groups but the effect was significantly higher in the BB-12 group; stool consistency was similar between the two groups. An increase in Bifidobacterium abundance (with significant correlation with crying time reduction), butyrate and HBD-2, LL-37, sIgA levels associated with a decrease in faecal calprotectin level were observed in the BB-12 group.

Conclusions: Supplementation with BB-12 is effective in managing infant colic. The effect could derive from immune and non-immune mechanisms associated with a modulation of gut microbiota structure and function.
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http://dx.doi.org/10.1111/apt.15561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973258PMC
January 2020

The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations.

Cell Host Microbe 2019 11 10;26(5):666-679.e7. Epub 2019 Oct 10.

CIBIO Department, University of Trento, 38123 Trento, Italy. Electronic address:

Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations.
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http://dx.doi.org/10.1016/j.chom.2019.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854460PMC
November 2019

Advancing integration of data on food microbiome studies: FoodMicrobionet 3.1, a major upgrade of the FoodMicrobionet database.

Int J Food Microbiol 2019 Sep 11;305:108249. Epub 2019 Jun 11.

Istituto di Scienze dell'Alimentazione-CNR, 83100 Avellino, Italy.

We present a new version of FoodMicrobionet, a database for the exploration of food bacterial communities. The database, available as an app built with the Shiny package of R, includes data from 44 studies and 2234 samples (food or food environment), covering dairy, meat, fruit and vegetables, cereal based and ready-to-eat foods. The interactive interface allows exploration of data, access to external resources (on line versions of the studies, sequence data on SRA, taxonomic databases), filtering samples on the basis of a number of criteria, aggregation of samples and bacterial taxa and export of data in a variety of formats. FoodMicrobionet is the largest collection of data on food bacterial communities and, due to the structure of sample metadata, largely derived from the European Food Safety Agency FoodEx2 classification, makes comparison and re-analysis of data from published and unpublished studies easy. Data exported from FoodMicrobionet can be readily used for graphical and statistical meta-analyses using open-source software (Gephi, Cytoscape, CoNet, and R packages and apps, such as phyloseq and Shiny-Phyloseq) thus providing scientists, risk assessors and industry with a wealth of information on the structure of food biomes.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2019.108249DOI Listing
September 2019

Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut-liver axis.

J Nutr Sci 2019 22;8:e15. Epub 2019 Apr 22.

Task Force on Microbiome Studies, University of Naples 'Federico II', Naples, Italy.

Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis ( < 0·01) and serum cholesterol ( < 0·001), alanine aminotransferase and glucose ( < 0·05). Accordingly, liver ( < 0·05) and acyl-CoA oxidase-1 ( < 0·05) as well as duodenal ATP-binding cassette (ABC) subfamily A1 () and subfamily G1 () ( < 0·05) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 ( < 0·05), duodenal claudin ( < 0·05) and duodenal peptide YY ( < 0·05) mRNA as well as a higher abundance of in the faeces ( < 0·05). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota.
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http://dx.doi.org/10.1017/jns.2019.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477661PMC
January 2020

Influence of microbial communities on the chemical and sensory features of Falanghina sweet passito wines.

Food Res Int 2019 06 19;120:740-747. Epub 2018 Nov 19.

Department of Agricultural Sciences, Division of Vine and Wine Sciences, University of Naples Federico II, Viale Italia, 83100 Avellino, Italy. Electronic address:

Natural (N) as well as starter inoculated (S, inoculated with Saccharomyces cerevisiae M3-5; CZS, Candida zemplinina T13, Zygosaccharomyces bailii NS113 and Saccharomyces cerevisiae M3-5) fermentations of Falanghina must from dehydrated grape were monitored. Culture dependent analyses and amplicon-based high-throughput sequencing targeting 18S rRNA and 16S rRNA genes were used to monitor the fungal and bacterial communities (8 sampling points during 65 days). The resulting wines were subject to both sensory evaluation and volatile organic compounds analysis. Fungal community of un-inoculated musts (N) at beginning of the fermentation was mainly represented by Aureobasidium, Cladosporium, Sclerotinia, while Candida, Debaryomyces, Hanseniaspora, Metschnikowia, Pichia, Saccharomyces and Zygosaccharomyces showed a very low occurrence. The dominance of Hanseniaspora vineae and/or Hanseniaspora uvarum was clear up to 29th days of fermentation. S. cerevisiae occurred in all the phases but become dominant only at the end of the process. The odour profiles as evaluate by Quantitative Descriptive Analysis (QDA) highlighted a significant impact of the fungal populations on the olfactory profiles of the wines. Raisins, dried fruits, Sherry and liqueur were stronger in both S and CZS, while N was mostly discriminated by solvent/chemical and floral features. Outcomes underpin the impact of microbiota on the chemical and odour traits of Falanghina passito wines.
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http://dx.doi.org/10.1016/j.foodres.2018.11.033DOI Listing
June 2019

Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain.

Brain Behav Immun 2020 03 3;85:128-141. Epub 2019 Apr 3.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address:

Recent evidence points to the gut microbiota as a regulator of brain and behavior, although it remains to be determined if gut bacteria play a role in chronic pain. The endocannabinoid system is implicated in inflammation and chronic pain processing at both the gut and central nervous system (CNS) levels. In the present study, we used low Vitamin D dietary intake in mice and evaluated possible changes in gut microbiota, pain processing and endocannabinoid system signaling. Vitamin D deficiency induced a lower microbial diversity characterized by an increase in Firmicutes and a decrease in Verrucomicrobia and Bacteroidetes. Concurrently, vitamin D deficient mice showed tactile allodynia associated with neuronal hyperexcitability and alterations of endocannabinoid system members (endogenous mediators and their receptors) at the spinal cord level. Changes in endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were also observed in the duodenum and colon. Remarkably, the anti-inflammatory anandamide congener, palmitoylethanolamide, counteracted both the pain behaviour and spinal biochemical changes in vitamin D deficient mice, whilst increasing the levels of Akkermansia, Eubacterium and Enterobacteriaceae, as compared with vehicle-treated mice. Finally, induction of spared nerve injury in normal or vitamin D deficient mice was not accompanied by changes in gut microbiota composition. Our data suggest the existence of a link between Vitamin D deficiency - with related changes in gut bacterial composition - and altered nociception, possibly via molecular mechanisms involving the endocannabinoid and related mediator signaling systems.
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http://dx.doi.org/10.1016/j.bbi.2019.04.006DOI Listing
March 2020

Probiotic potential of a Lactobacillus rhamnosus cheese isolate and its effect on the fecal microbiota of healthy volunteers.

Food Res Int 2019 05 5;119:305-314. Epub 2019 Feb 5.

Department of Agricultural, Forest and Food Sciences, University of Torino, Italy. Electronic address:

The present study describes an in vitro characterization of strains of lactic acid bacteria, focusing on physiological characters of probiotic interest, and a subsequent placebo-controlled, crossover administration trial, with a cohort of healthy volunteers. The strains of lactic acid bacteria were previously isolated from a fermented food (ripened cheese) and several ones resulted to have promising probiotic characteristics. Based on comprehensive evaluation of the data obtained, one strain was chosen and supplemented in a fermented milk. The fermented milk was then used in the administration trial with the goal of assessing its effect on the composition of the intestinal microbiota, as reflected in the feces. The fermented milk, with or without probiotic, had an effect on the intestinal microbiota and significant inter-individual differences were observed in response to the intervention. A common trend was observed related to two important populations of the human gut microbiota; a reduction in the relative abundance of Bacteroides and increase in the abundance of Prevotella in subjects during treatment compared to baseline were registered.
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http://dx.doi.org/10.1016/j.foodres.2019.02.004DOI Listing
May 2019
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