Giulia Longhi

University of Parma

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Marco Ventura

University of Parma

Leonardo Mancabelli

University of Parma

Francesca Turroni

University of Parma

Christian Milani

University of Parma

Gabriele Andrea Lugli

University of Parma

Giulia Alessandri

University of Siena

Rosaria Anzalone

University of Parma

Douwe van Sinderen

University College Cork

Alice Viappiani

University of Parma

Federico Fontana

University of Parma

Cooperative Institutions

University of Parma

University of Cagliari

Instituto de Productos Lácteos de Asturias

Instituto de Investigación Sanitaria del Principado de Asturias

Consejo Superior de Investigaciones Científicas

University of Milan

Azienda Ospedaliero-Universitaria Cagliari

Ecogenomics (Japan)

University of Padua

Czech University of Life Sciences Prague

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Designation of optimal reference strains representing the infant gut bifidobacterial species through a comprehensive multi‐omics approach

Environmental Microbiology (2022)

Federico Fontana Giulia Alessandri Chiara Tarracchini Massimiliano G. Bianchi Sonia Mirjam Rizzo

Abstract The genomic era has resulted in the generation of a massive amount of genetic data concerning the genomic diversity of bacterial taxa. As a result, the microbiological community is increasingly looking for ways to define reference bacterial strains to perform experiments that are representative of the entire bacterial species. Despite this, there is currently no established approach allowing a reliable identification of reference strains based on a comprehensive genomic, ecological, and functional context. In the current study, we developed a comprehensive multi‐omics approach that will allow the identification of the optimal reference strains using the Bifidobacterium genus as test case. Strain tracking analysis based on 1664 shotgun metagenomics datasets of healthy infant faecal samples were employed to identify bifidobacterial strains suitable for in silico and in vitro analyses. Subsequently, an ad hoc bioinformatic tool was developed to screen local strain collections for the most suitable species‐representative strain alternative. The here presented approach was validated using in vitro trials followed by metagenomics and metatranscriptomics analyses. Altogether, these results demonstrated the validity of the proposed model for reference strain selection, thus allowing improved in silico and in vitro investigations both in terms of cross‐laboratory reproducibility and relevance of research findings.

Identification

Strain (injury)

10.1111/1462-2920.16205

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Citations (10)

Microbiota and Cancer: The Emerging Beneficial Role of Bifidobacteria in Cancer Immunotherapy

Frontiers in Microbiology (2020)

Giulia Longhi Douwe van Sinderen Marco Ventura Francesca Turroni

Many intestinal bacteria are believed to be involved in various inflammatory and immune processes that influence tumor etiology because of their metabolic properties and their ability to alter the microbiota homeostasis. Although many functions of the microbiota are still unclear, there is compelling experimental evidence showing that the intestinal microbiota is able to modulate carcinogenesis and the response to anticancer therapies, both in the intestinal tract and other body sites. Among the wide variety of gut-colonizing microorganisms, various species belonging to the Bifidobacterium genus are believed to elicit beneficial effects on human physiology and on the host-immune system. Recent findings, based on preclinical mouse models and on human clinical trials, have demonstrated the impact of gut commensals including bifidobacteria on the efficacy of tumour-targeting immunotherapy. Although the underlying molecular mechanisms remain obscure, bifidobacteria and other microorganisms have become a promising aid to immunotherapeutic procedures that are currently applied to treat cancer. The present review focuses on strategies to recruit the microbiome in order to enhance anticancer responses and develop therapies aimed at fighting the onset and progression of malignancies.

Commensalism

Cancer Immunotherapy

10.3389/fmicb.2020.575072

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Citations (56)

Genomic and ecological approaches to identify the Bifidobacterium breve prototype of the healthy human gut microbiota

Frontiers in Microbiology (2024)

Chiara Argentini Gabriele Andrea Lugli Chiara Tarracchini Federico Fontana Leonardo Mancabelli

Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guided by ecology- and phylogenome-based analyses, was employed to identify a representative strain of B. breve to be exploited as a novel health-promoting candidate. The selected strain, i.e., B. breve PRL2012, was found to well represent the genetic content and functional genomic features of the B. breve taxon. We evaluated the ability of PRL2012 to survive in the gastrointestinal tract and to interact with other human gut commensal microbes. When co-cultivated with various human gut commensals, B. breve PRL2012 revealed an enhancement of its metabolic activity coupled with the activation of cellular defense mechanisms to apparently improve its survivability in a simulated ecosystem resembling the human microbiome.

Bifidobacterium breve

Human gastrointestinal tract

Commensalism

Gut microbiome

Strain (injury)

10.3389/fmicb.2024.1349391

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The Probiotic Identity Card: A Novel “Probiogenomics” Approach to Investigate Probiotic Supplements

Frontiers in Microbiology (2022)

Gabriele Andrea Lugli Giulia Longhi Giulia Alessandri Leonardo Mancabelli Chiara Tarracchini

Probiotic bacteria are widely administered as dietary supplements and incorporated as active ingredients in a variety of functional foods due to their purported health-promoting features. Currently available probiotic products may have issues with regards to their formulation, such as insufficient levels of viable probiotic bacteria, complete lack of probiotic strains that are stated to be present in the product, and the presence of microbial contaminants. To avoid the distribution of such unsuitable or misleading products, we propose here a novel approach named Probiotic Identity Card (PIC), involving a combination of shotgun metagenomic sequencing and bacterial cell enumeration by flow cytometry. PIC was tested on 12 commercial probiotic supplements revealing several inconsistencies in the formulation of five such products based on their stated microbial composition and viability.

Health Benefits

10.3389/fmicb.2021.790881

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Contribution of the capsular polysaccharide layer to antibiotic resistance in bifidobacteria

FEMS Microbiology Ecology (2023)

Chiara Argentini Chiara Tarracchini Giulia Alessandri Giulia Longhi Christian Milani

Abstract Bifidobacteria have been shown to produce exopolysaccharides (EPS), which are polymeric structures composed of various carbohydrates, commonly containing glucose, galactose, and rhamnose. EPS are produced by different bifidobacterial taxa commonly identified in the human gut, such as Bifidobacterium breve and Bifidobacterium longum subsp. longum, and have been suggested to modulate the interaction of bifidobacterial cells with other members of the human gut microbiota as well as with their host. In this study, we evaluated if bifidobacterial EPS production of four selected EPS-producing strains is associated with enhanced resistance to antibiotic treatments through MIC analysis when compared to bacterial cultures that do not produce exopolysaccharides. Our results showed that an increase in EPS production by modifying the growth medium with different carbon sources, i.e. glucose, galactose or lactose and/or by applying stressful conditions, such as bile salts and acidity, is associated with a tolerance enhancement of bifidobacterial cells toward various beta-lactam antibiotics. In addition, after analyzing the production of EPS at the phenotypic level, we explored the genes involved in the production of these structures and evaluated their expression, in presence of various carbon sources, using RNAseq. Overall, this study provides preliminary experimental evidence showing how bifidobacterial EPS modifies the level of susceptibility of these bacteria towards antibiotics.

Bifidobacterium breve

Bifidobacterium longum

Actinomycetaceae

Rhamnose

10.1093/femsec/fiad032

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Citations (2)

Investigating bifidobacteria and human milk oligosaccharide composition of lactating mothers

FEMS Microbiology Ecology (2020)

Gabriele Andrea Lugli Sabrina Duranti Christian Milani Leonardo Mancabelli Francesca Turroni

ABSTRACT Human milk is known to carry its own microbiota, of which the precise origin remains obscure. Breastfeeding allows mother-to-baby transmission of microorganisms as well as the transfer of many other milk components, such as human milk oligosaccharides (HMOs), which act as metabolizable substrates for particular bacteria, such as bifidobacteria, residing in infant intestinal tract. In the current study, we report the HMO composition of 249 human milk samples, in 163 of which we quantified the abundance of members of the Bifidobacterium genus using a combination of metagenomic and flow cytometric approaches. Metagenomic data allowed us to identify four clusters dominated by Bifidobacterium adolescentis and Bifidobacterium pseudolongum, Bifidobacterium crudilactis or Bifidobacterium dentium, as well as a cluster represented by a heterogeneous mix of bifidobacterial species such as Bifidobacterium breve and Bifidobacterium longum. Furthermore, in vitro growth assays on HMOs coupled with in silico glycobiome analyses allowed us to elucidate that members of the Bifidobacterium bifidum and B. breve species exhibit the greatest ability to degrade and grow on HMOs. Altogether, these findings indicate that the bifidobacterial component of the human milk microbiota is not strictly correlated with their ability to metabolize HMOs.

Bifidobacterium longum

Bifidobacterium breve

Bifidobacterium bifidum

Actinomycetaceae

Human gastrointestinal tract

10.1093/femsec/fiaa049

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Probiogenomics Analysis of 97 Lactobacillus crispatus Strains as a Tool for the Identification of Promising Next-Generation Probiotics

Microorganisms (2020)

Federico Fontana Giulia Alessandri Gabriele Andrea Lugli Leonardo Mancabelli Giulia Longhi

Members of the genus Lactobacillus represent the most common colonizers of the human vagina and are well-known for preserving vaginal health and contrasting the colonization of opportunistic pathogens. Remarkably, high abundance of Lactobacillus crispatus in the vaginal environment has been linked to vaginal health, leading to the widespread use of many L. crispatus strains as probiotics. Nevertheless, despite the scientific and industrial relevance of this species, a comprehensive investigation of the genomics of L. crispatus taxon is still missing. For this reason, we have performed a comparative genomics analysis of 97 L. crispatus strains, encompassing 16 strains sequenced in the framework of this study alongside 81 additional publicly available genome sequences. Thus, allowing the dissection of the L.crispatus pan-genome and core-genome followed by a comprehensive phylogenetic analysis based on the predicted core genes that revealed clustering based on ecological origin. Subsequently, a genomics-targeted approach, i.e., probiogenomics analysis, was applied for in-depth analysis of the eight L. crispatus strains of human origin sequenced in this study. In detail their genetic repertoire was screened for strain-specific genes responsible for phenotypic features that may guide the identification of optimal candidates for next-generation probiotics. The latter includes bacteriocin production, carbohydrates transport and metabolism, as well as a range of features that may be responsible for improved ecological fitness. In silico results regarding the genetic repertoire involved in carbohydrate metabolism were also validated by growth assays on a range of sugars, leading to the selection of putative novel probiotic strains.

Lactobacillus crispatus

Comparative Genomics

10.3390/microorganisms9010073

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Citations (14)

Untangling Species-Level Composition of Complex Bacterial Communities through a Novel Metagenomic Approach

mSystems (2020)

Christian Milani Giulia Alessandri Marta Mangifesta Leonardo Mancabelli Gabriele Andrea Lugli

16S small-subunit (SSU) rRNA gene-based bacterial profiling is the gold standard for cost-effective taxonomic reconstruction of complex bacterial populations down to the genus level. However, it has been proven ineffective in clinical and research settings requiring higher taxonomic resolution. We therefore developed a bacterial profiling method based on the internal transcribed spacer (ITS) region employing optimized primers and a comprehensive ITS database for accurate cataloguing of bacterial communities at (sub)species resolution. Performance of the microbial ITS profiling pipeline was tested through analysis of host-associated, food, and environmental matrices, while its efficacy in clinical settings was assessed through analysis of mucosal biopsy specimens of colorectal cancer, leading to the identification of putative novel biomarkers. The data collected indicate that the proposed pipeline represents a major step forward in cost-effective identification and screening of microbial biomarkers at (sub)species level, with relevant impact in research, industrial, and clinical settings.IMPORTANCE We developed a novel method for accurate cataloguing of bacterial communities at (sub)species level involving amplification of the internal transcribed spacer (ITS) region through optimized primers, followed by next-generation sequencing and taxonomic classification of amplicons by means of a comprehensive database of bacterial ITS sequences. Host-associated, food, and environmental matrices were employed to test the performance of the microbial ITS profiling pipeline. Moreover, mucosal biopsy samples from colorectal cancer patients were analyzed to demonstrate the scientific relevance of this profiling approach in a clinical setting through identification of putative novel biomarkers. The results indicate that the ITS-based profiling pipeline proposed here represents a key metagenomic tool with major relevance for research, industrial, and clinical settings.

Amplicon

Profiling (computer programming)

Biological classification

10.1128/msystems.00404-20

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Citations (13)

Identification of a prototype human gut Bifidobacterium longum subsp. longum strain based on comparative and functional genomic approaches

Frontiers in Microbiology (2023)

Giulia Alessandri Federico Fontana Chiara Tarracchini Sonia Mirjam Rizzo Massimiliano G. Bianchi

Bifidobacteria are extensively exploited for the formulation of probiotic food supplements due to their claimed ability to exert health-beneficial effects upon their host. However, most commercialized probiotics are tested and selected for their safety features rather than for their effective abilities to interact with the host and/or other intestinal microbial players. In this study, we applied an ecological and phylogenomic-driven selection to identify novel B. longum subsp. longum strains with a presumed high fitness in the human gut. Such analyses allowed the identification of a prototype microorganism to investigate the genetic traits encompassed by the autochthonous bifidobacterial human gut communities. B. longum subsp. longum PRL2022 was selected due to its close genomic relationship with the calculated model representative of the adult human-gut associated B. longum subsp. longum taxon. The interactomic features of PRL2022 with the human host as well as with key representative intestinal microbial members were assayed using in vitro models, revealing how this bifidobacterial gut strain is able to establish extensive cross-talk with both the host and other microbial residents of the human intestine.

Bifidobacterium longum

Identification

Strain (injury)

10.3389/fmicb.2023.1130592

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Citations (7)

Characterization of the phylogenetic diversity of two novel species belonging to the genus Bifidobacterium: Bifidobacterium cebidarum sp. nov. and Bifidobacterium leontopitheci sp. nov.

INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY (2020)

Sabrina Duranti Gabriele Andrea Lugli Alice Viappiani Leonardo Mancabelli Giulia Alessandri

Two Bifidobacterium strains, i.e., 2176BT and 2177BT, were isolated from Golden-Headed Lion Tamarin (Leontopithecus chrysomelas) and Goeldi's monkey (Callimico goeldii). Isolates were shown to be Gram-positive, non-motile, non-sporulating, facultative anaerobic and d-fructose 6-phosphate phosphoketolase-positive. Phylogenetic analyses based on 16S rRNA sequences, multilocus sequences (including hsp60, rpoB, dnaJ, dnaG and clpC genes) and the core genome revealed that bifidobacterial strains 2176BT and 2177BT exhibit close phylogenetic relatedness to Bifidobacterium felsineum DSM 103139T and Bifidobacterium bifidum LMG 11041T, respectively. Further genotyping based on the genome sequence of the isolated strains combined with phenotypic analyses, clearly show that these strains are distinct from each of the type strains of the so far recognized Bifidobacterium species. Thus, Bifidobacterium cebidarum sp. nov. (2176BT=LMG 31469T=CCUG 73785T) and Bifidobacterium leontopitheci sp. nov. (2177BT=LMG 31471T=CCUG 73786T are proposed as novel Bifidobacterium species.

Bifidobacterium bifidum

Multilocus sequence typing

10.1099/ijsem.0.004032

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Citations (23)