Special Issue "Bifidobacteria: Insights from Ecology to Genomics of a Key Microbial Group of the Mammalian Gut Microbiota"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (30 November 2019).

Special Issue Editors

Prof. Dr. Marco Ventura
E-Mail Website
Guest Editor
Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
Interests: molecular analysis of bifidobacteria; diversity and host significance of gut microbiota
Prof. Dr. Douwe van Sinderen
E-Mail Website
Guest Editor
University College Cork, APC Microbiome Ireland, Cork, Ireland
Interests: gut microbiota; comparative and functional genomics; molecular microbiology; bacteriophages; human gut commensal bacteria
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Turroni
E-Mail Website
Guest Editor
Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
Interests: bifidobacteria; human and mammalian microbiota; intestinal host-microbe interaction; microbiota of raw milk cheese
Dr. Jennifer Mahony
E-Mail Website
Guest Editor
APC Microbiome Institute and School of Microbiology, Bioscience Institute, National University of Ireland, Cork, Ireland
Interests: phage–host interactions; food microbiology; functional genomics
Special Issues, Collections and Topics in MDPI journals
Dr. Christian Milani
E-Mail
Guest Editor
Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental Sustainability, University of Parma, Parma, Italy
Interests: metagenomics; microbial Genomics; microbiota
Dr. Francesca Bottacini
E-Mail Website
Guest Editor
Department of Biological Sciences, Munster Technological University, Bishopstown, Cork­, Ireland
Interests: gut microbiota; genomics and ecology of bifidobacteria and lactic acid bacteria; probiotics; food microbiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, scientists have invested a very significant amount of effort into dissecting the composition of the microbial community in the human gut and the interactions with their host, the latter being a crucial factor in host physiology and associated metabolic activities. In this context, the presence of members of the genus Bifidobacterium within this gut microbiota have consistently been associated with positive health implications towards the host. These commensal bacteria are among the first colonizers of the human gut, partly through a demonstrated vertical transmission route from mother to newborn. The colonization and establishment of these bacteria in the human gut is modulated by specific human milk constituents according to a fascinating mechanism of microbe–host co-evolution. It has been shown that bifidobacterial genomes have evolved to acquire a specific gene arsenal towards the utilization of specific carbohydrate components of this human excretion. The biology of bifidobacteria has been extensively exploited and several of their saccharolytic features are well characterized. Furthermore, a number of studies have highlighted the intricate relationships of bifidobacteria with their human host, as well as other members of the gut microbiota. Notably, the ecological role of bifidobacteria as part of the human gut microbiota has been investigated in terms of shaping the gut microbiota and re-establishment of microbiota homeostasis through cross-feeding activities.

This Special Issue of Microorganisms will cover relevant and recent information on this topic, in order to generate a comprehensive overview of the biology of bifidobacteria.

Prof. Dr. Marco Ventura
Dr. Douwe van Sinderen
Dr. Francesca Turroni
Dr. Jennifer Mahony
Dr. Christian Milani
Dr. Francesca Bottacini
Guest Editors

Manuscript Submission Information

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Published Papers (14 papers)

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Editorial

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Editorial
Special Issue “Bifidobacteria: Insights from Ecology to Genomics of a Key Microbial Group of the Mammalian Gut Microbiota”
Microorganisms 2020, 8(11), 1660; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8111660 - 27 Oct 2020
Viewed by 671
Abstract
In recent years, substantial efforts have been made to dissect the composition of microbial communities that are present in the human gut, and to investigate their interactions with their host [...] Full article

Research

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Article
Donated Human Milk as a Determinant Factor for the Gut Bifidobacterial Ecology in Premature Babies
Microorganisms 2020, 8(5), 760; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8050760 - 19 May 2020
Cited by 5 | Viewed by 1497
Abstract
Correct establishment of the gut microbiome is compromised in premature babies, with Bifidobacterium being one of the most affected genera. Prematurity often entails the inability to successfully breastfeed, therefore requiring the implementation of other feeding modes; breast milk expression from a donor mother [...] Read more.
Correct establishment of the gut microbiome is compromised in premature babies, with Bifidobacterium being one of the most affected genera. Prematurity often entails the inability to successfully breastfeed, therefore requiring the implementation of other feeding modes; breast milk expression from a donor mother is the recommended option when their own mother’s milk is not available. Some studies showed different gut microbial profiles in premature infants fed with breast milk and donor human milk, however, it is not known how this affects the species composition of the genus Bifidobacterium. The objective of this study was to assess the effect of donated human milk on shaping the gut bifidobacterial populations of premature babies during the first three months of life. We analyzed the gut bifidobacterial communities of 42 premature babies fed with human donor milk or own-mother milk by the 16S rRNA–23S rRNA internal transcriber spaces (ITS) region sequencing and q-PCR. Moreover, metabolic activity was assessed by gas chromatography. We observed a specific bifidobacterial profile based on feeding type, with higher bifidobacterial diversity in the human donor milk group. Differences in specific Bifidobacterium species composition may contribute to the development of specific new strategies or treatments aimed at mimicking the impact of own-mother milk feeding in neonatal units. Full article
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Article
Revisiting the Metabolic Capabilities of Bifidobacterium longum susbp. longum and Bifidobacterium longum subsp. infantis from a Glycoside Hydrolase Perspective
Microorganisms 2020, 8(5), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8050723 - 13 May 2020
Cited by 6 | Viewed by 1409
Abstract
Bifidobacteria are among the most abundant microorganisms inhabiting the intestine of humans and many animals. Within the genus Bifidobacterium, several beneficial effects have been attributed to strains belonging to the subspecies Bifidobacterium longum subsp. longum and Bifidobacterium longum subsp. infantis, which [...] Read more.
Bifidobacteria are among the most abundant microorganisms inhabiting the intestine of humans and many animals. Within the genus Bifidobacterium, several beneficial effects have been attributed to strains belonging to the subspecies Bifidobacterium longum subsp. longum and Bifidobacterium longum subsp. infantis, which are often found in infants and adults. The increasing numbers of sequenced genomes belonging to these two subspecies, and the availability of novel computational tools focused on predicting glycolytic abilities, with the aim of understanding the capabilities of degrading specific carbohydrates, allowed us to depict the potential glycoside hydrolases (GH) of these bacteria, with a focus on those GH profiles that differ in the two subspecies. We performed an in silico examination of 188 sequenced B. longum genomes and depicted the commonly present and strain-specific GHs and GH families among representatives of this species. Additionally, GH profiling, genome-based and 16S rRNA-based clustering analyses showed that the subspecies assignment of some strains does not properly match with their genetic background. Furthermore, the analysis of the potential GH component allowed the distinction of clear GH patterns. Some of the GH activities, and their link with the two subspecies under study, are further discussed. Overall, our in silico analysis poses some questions about the suitability of considering the GH activities of B. longum subsp. longum and B. longum subsp. infantis to gain insight into the characterization and classification of these two subspecies with probiotic interest. Full article
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Article
Comprehensive Mining and Characterization of CRISPR-Cas Systems in Bifidobacterium
Microorganisms 2020, 8(5), 720; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8050720 - 12 May 2020
Cited by 9 | Viewed by 1764
Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated cas) systems constitute the adaptive immune system in prokaryotes, which provides resistance against bacteriophages and invasive genetic elements. The landscape of applications in bacteria and eukaryotes relies on a few Cas effector proteins [...] Read more.
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated cas) systems constitute the adaptive immune system in prokaryotes, which provides resistance against bacteriophages and invasive genetic elements. The landscape of applications in bacteria and eukaryotes relies on a few Cas effector proteins that have been characterized in detail. However, there is a lack of comprehensive studies on naturally occurring CRISPR-Cas systems in beneficial bacteria, such as human gut commensal Bifidobacterium species. In this study, we mined 954 publicly available Bifidobacterium genomes and identified CRIPSR-Cas systems in 57% of these strains. A total of five CRISPR-Cas subtypes were identified as follows: Type I-E, I-C, I-G, II-A, and II-C. Among the subtypes, Type I-C was the most abundant (23%). We further characterized the CRISPR RNA (crRNA), tracrRNA, and PAM sequences to provide a molecular basis for the development of new genome editing tools for a variety of applications. Moreover, we investigated the evolutionary history of certain Bifidobacterium strains through visualization of acquired spacer sequences and demonstrated how these hypervariable CRISPR regions can be used as genotyping markers. This extensive characterization will enable the repurposing of endogenous CRISPR-Cas systems in Bifidobacteria for genome engineering, transcriptional regulation, genotyping, and screening of rare variants. Full article
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Article
Application of Recombinase-Based In Vivo Expression Technology to Bifidobacterium longum subsp. longum for Identification of Genes Induced in the Gastrointestinal Tract of Mice
Microorganisms 2020, 8(3), 410; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8030410 - 13 Mar 2020
Cited by 4 | Viewed by 1887
Abstract
Bifidobacteria are one of the major components in human gut microbiota and well-known as beneficial microbes. However, clarification of commensal mechanisms of bifidobacteria in the intestines is still ongoing, especially in the presence of the gut microbiota. Here, we applied recombinase-based in vivo [...] Read more.
Bifidobacteria are one of the major components in human gut microbiota and well-known as beneficial microbes. However, clarification of commensal mechanisms of bifidobacteria in the intestines is still ongoing, especially in the presence of the gut microbiota. Here, we applied recombinase-based in vivo expression technology (R-IVET) using the bacteriophage P1 Cre/loxP system to Bifidobacterium longum subsp. longum 105-A (B. longum 105-A) to identify genes that are specifically expressed in the gastrointestinal tract of conventionally raised mice. Oral administration of the genomic DNA library of B. longum 105-A to conventionally raised mice resulted in the identification of 73 in vivo-induced genes. Four out of seven tested genes were verified in vivo-specific induction at least in the cecum by quantitative reverse transcription PCR. Although there is still room for improvement of the system, our findings can contribute to expanding our understanding of the commensal behavior of B. longum in the gut ecosystem. Full article
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Article
Potential Effects of Indole-3-Lactic Acid, a Metabolite of Human Bifidobacteria, on NGF-Induced Neurite Outgrowth in PC12 Cells
Microorganisms 2020, 8(3), 398; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8030398 - 12 Mar 2020
Cited by 20 | Viewed by 1720
Abstract
Gut microbiota-derived tryptophan metabolites such as indole derivatives are an integral part of host metabolome that could mediate gut–brain communication and contribute to host homeostasis. We previously reported that infant-type Human-Residential Bifidobacteria (HRB) produced higher levels of indole-3-lactic acid (ILA), suggesting the former [...] Read more.
Gut microbiota-derived tryptophan metabolites such as indole derivatives are an integral part of host metabolome that could mediate gut–brain communication and contribute to host homeostasis. We previously reported that infant-type Human-Residential Bifidobacteria (HRB) produced higher levels of indole-3-lactic acid (ILA), suggesting the former might play a specific role in microbiota–host crosstalk by producing ILA in human infants. Nonetheless, the biological meaning of bifidobacteria-derived ILA in infant health development remains obscure. Here, we sought to explore the potential role of ILA in neuronal differentiation. We examined the neurite outgrowth and acetylcholinesterase (AchE) activity of PC12 cells following exposure to ILA and NGF induction. We found that ILA substantially enhanced NGF-induced neurite outgrowth of PC12 cells in a dose-dependent manner, and had the most prominent effect at 100 nM. Significant increases in the expression of TrkA receptor, ERK1/2 and CREB were observed in ILA-treated PC12 cells, suggesting ILA potentiated NGF-induced neurite outgrowth through the Ras/ERK pathway. Additionally, ILA was found to act as the aryl hydrocarbon receptor (AhR) agonist and evoked NGF-induced neurite outgrowth in an AhR-mediated manner. These new findings provide clues into the potential involvement of ILA as the mediator in bifidobacterial host–microbiota crosstalk and neuronal developmental processes. Full article
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Article
The Impact of Primer Design on Amplicon-Based Metagenomic Profiling Accuracy: Detailed Insights into Bifidobacterial Community Structure
Microorganisms 2020, 8(1), 131; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8010131 - 17 Jan 2020
Cited by 16 | Viewed by 1455
Abstract
Next Generation Sequencing (NGS) technologies have overcome the limitations of cultivation-dependent approaches and allowed detailed study of bacterial populations that inhabit the human body. The consortium of bacteria residing in the human intestinal tract, also known as the gut microbiota, impacts several physiological [...] Read more.
Next Generation Sequencing (NGS) technologies have overcome the limitations of cultivation-dependent approaches and allowed detailed study of bacterial populations that inhabit the human body. The consortium of bacteria residing in the human intestinal tract, also known as the gut microbiota, impacts several physiological processes important for preservation of the health status of the host. The most widespread microbiota profiling method is based on amplification and sequencing of a variable portion of the 16S rRNA gene as a universal taxonomic marker among members of the Bacteria domain. Despite its popularity and obvious advantages, this 16S rRNA gene-based approach comes with some important limitations. In particular, the choice of the primer pair for amplification plays a major role in defining the accuracy of the reconstructed bacterial profiles. In the current study, we performed an in silico PCR using all currently described 16S rRNA gene-targeting primer pairs (PP) in order to assess their efficiency. Our results show that V3, V4, V5, and V6 were the optimal regions on which to design 16S rRNA metagenomic primers. In detail, PP39 (Probio_Uni/Probio_Rev), PP41 (341F/534R), and PP72 (970F/1050R) were the most suitable primer pairs with an amplification efficiency of >98.5%. Furthermore, the Bifidobacterium genus was examined as a test case for accurate evaluation of intra-genus performances at subspecies level. Intriguingly, the in silico analysis revealed that primer pair PP55 (527f/1406r) was unable to amplify the targeted region of any member of this bacterial genus, while several other primer pairs seem to rather inefficiently amplify the target region of the main bifidobacterial taxa. These results highlight that selection of a 16S rRNA gene-based PP should be done with utmost care in order to avoid biases in microbiota profiling results. Full article
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Article
Comparative Pangenomics of the Mammalian Gut Commensal Bifidobacterium longum
Microorganisms 2020, 8(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8010007 - 18 Dec 2019
Cited by 12 | Viewed by 1613
Abstract
Bifidobacterium longum colonizes mammalian gastrointestinal tracts where it could metabolize host-indigestible oligosaccharides. Although B. longum strains are currently segregated into three subspecies that reflect common metabolic capacities and genetic similarity, heterogeneity within subspecies suggests that these taxonomic boundaries may not be completely resolved. [...] Read more.
Bifidobacterium longum colonizes mammalian gastrointestinal tracts where it could metabolize host-indigestible oligosaccharides. Although B. longum strains are currently segregated into three subspecies that reflect common metabolic capacities and genetic similarity, heterogeneity within subspecies suggests that these taxonomic boundaries may not be completely resolved. To address this, the B. longum pangenome was analyzed from representative strains isolated from a diverse set of sources. As a result, the B. longum pangenome is open and contains almost 17,000 genes, with over 85% of genes found in ≤28 of 191 strains. B. longum genomes share a small core gene set of only ~500 genes, or ~3% of the total pangenome. Although the individual B. longum subspecies pangenomes share similar relative abundances of clusters of orthologous groups, strains show inter- and intrasubspecies differences with respect to carbohydrate utilization gene content and growth phenotypes. Full article
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Article
Mobilome and Resistome Reconstruction from Genomes Belonging to Members of the Bifidobacterium Genus
Microorganisms 2019, 7(12), 638; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7120638 - 02 Dec 2019
Cited by 12 | Viewed by 1686
Abstract
Specific members of the genus Bifidobacterium are among the first colonizers of the human/animal gut, where they act as important intestinal commensals associated with host health. As part of the gut microbiota, bifidobacteria may be exposed to antibiotics, used in particular for intrapartum [...] Read more.
Specific members of the genus Bifidobacterium are among the first colonizers of the human/animal gut, where they act as important intestinal commensals associated with host health. As part of the gut microbiota, bifidobacteria may be exposed to antibiotics, used in particular for intrapartum prophylaxis, especially to prevent Streptococcus infections, or in the very early stages of life after the birth. In the current study, we reconstructed the in silico resistome of the Bifidobacterium genus, analyzing a database composed of 625 bifidobacterial genomes, including partial assembled strains with less than 100 genomic sequences. Furthermore, we screened bifidobacterial genomes for mobile genetic elements, such as transposases and prophage-like elements, in order to investigate the correlation between the bifido-mobilome and the bifido-resistome, also identifying genetic insertion hotspots that appear to be prone to horizontal gene transfer (HGT) events. These insertion hotspots were shown to be widely distributed among analyzed bifidobacterial genomes, and suggest the acquisition of antibiotic resistance genes through HGT events. These data were further corroborated by growth experiments directed to evaluate bacitracin A resistance in Bifidobacterium spp., a property that was predicted by in silico analyses to be part of the HGT-acquired resistome. Full article
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Article
Bifidobacterial Distribution Across Italian Cheeses Produced from Raw Milk
Microorganisms 2019, 7(12), 599; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7120599 - 21 Nov 2019
Cited by 6 | Viewed by 1210
Abstract
Cheese microbiota is of high industrial relevance due to its crucial role in defining the organoleptic features of the final product. Nevertheless, the composition of and possible microbe–microbe interactions between these bacterial populations have never been assessed down to the species-level. For this [...] Read more.
Cheese microbiota is of high industrial relevance due to its crucial role in defining the organoleptic features of the final product. Nevertheless, the composition of and possible microbe–microbe interactions between these bacterial populations have never been assessed down to the species-level. For this reason, 16S rRNA gene microbial profiling combined with internally transcribed spacer (ITS)-mediated bifidobacterial profiling analyses of various cheeses produced with raw milk were performed in order to achieve an in-depth view of the bifidobacterial populations present in these microbially fermented food matrices. Moreover, statistical elaboration of the data collected in this study revealed the existence of community state types characterized by the dominance of specific microbial genera that appear to shape the overall cheese microbiota through an interactive network responsible for species-specific modulatory effects on the bifidobacterial population. Full article
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Article
Uncovering Bifidobacteria via Targeted Sequencing of the Mammalian Gut Microbiota
Microorganisms 2019, 7(11), 535; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7110535 - 06 Nov 2019
Cited by 4 | Viewed by 1024
Abstract
Bifidobacteria are among the most prevalent gut commensals in mammals, playing crucial functional roles that start from their early colonization of the infant gastrointestinal tract and last throughout the life span of their host. Metagenomic approaches have been employed to unveil the genetic [...] Read more.
Bifidobacteria are among the most prevalent gut commensals in mammals, playing crucial functional roles that start from their early colonization of the infant gastrointestinal tract and last throughout the life span of their host. Metagenomic approaches have been employed to unveil the genetic features of bifidobacteria in order to understand how they participate in the correct development of a healthy microbiome. Nevertheless, their low relative abundance in many environmental samples may represent a major limitation for metagenomics approaches. To overcome this restriction, we applied an enrichment method that allows amplification of bifidobacterial DNA obtained from human or animal fecal samples for up to 26,500-fold, resulting in the metagenomic reconstruction of genomes belonging to bifidobacterial strains, present at very low abundance in collected samples. Functional predictions of the genes from these reconstructed genomes allows us to identify unique signatures among members of the same bifidobacterial species, highlighting genes correlated with the uptake of nutrients and adhesion to the intestinal mucosa. Full article
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Communication
Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated fromHuman Infants
Microorganisms 2019, 7(9), 340; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7090340 - 11 Sep 2019
Cited by 26 | Viewed by 1856
Abstract
Recent studies have shown that metabolites produced by microbes can be considered as mediators of host-microbial interactions. In this study, we examined the production of tryptophan metabolites by Bifidobacterium strains found in the gastrointestinal tracts of humans and other animals. Indole-3-lactic acid (ILA) [...] Read more.
Recent studies have shown that metabolites produced by microbes can be considered as mediators of host-microbial interactions. In this study, we examined the production of tryptophan metabolites by Bifidobacterium strains found in the gastrointestinal tracts of humans and other animals. Indole-3-lactic acid (ILA) was the only tryptophan metabolite produced in bifidobacteria culture supernatants. No others, including indole-3-propionic acid, indole-3-acetic acid, and indole-3-aldehyde, were produced. Strains of bifidobacterial species commonly isolated from the intestines of human infants, such as Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Bifidobacterium bifidum, produced higher levels of ILA than did strains of other species. These results imply that infant-type bifidobacteria might play a specific role in host–microbial cross-talk by producing ILA in human infants. Full article
Article
Bifidobacterial Transfer from Mother to Child as Examined by an Animal Model
Microorganisms 2019, 7(9), 293; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7090293 - 27 Aug 2019
Cited by 7 | Viewed by 1235
Abstract
Bifidobacteria commonly constitute the most abundant group of microorganisms in the healthy infant gut. Their intestinal establishment is believed to be maternally driven, and their acquisition has even been postulated to occur during pregnancy. In the current study, we evaluated bifidobacterial mother-to infant [...] Read more.
Bifidobacteria commonly constitute the most abundant group of microorganisms in the healthy infant gut. Their intestinal establishment is believed to be maternally driven, and their acquisition has even been postulated to occur during pregnancy. In the current study, we evaluated bifidobacterial mother-to infant transmission events in a rat model by means of quantitative PCR (qPCR), as well as by Internally Transcribed Spacer (ITS) bifidobacterial profiling. The occurrence of strains supplied by mothers during pregnancy to their corresponding newborns was observed and identified by analysis immediately following C-section delivery. These findings provide intriguing support for the existence of an unknown route to facilitate bifidobacterial transfer during the very early stages of life. Full article
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Review

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Review
Bifidobacterium bifidum: A Key Member of the Early Human Gut Microbiota
Microorganisms 2019, 7(11), 544; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms7110544 - 09 Nov 2019
Cited by 25 | Viewed by 3050
Abstract
Bifidobacteria typically represent the most abundant bacteria of the human gut microbiota in healthy breast-fed infants. Members of the Bifidobacterium bifidum species constitute one of the dominant taxa amongst these bifidobacterial communities and have been shown to display notable physiological and genetic features [...] Read more.
Bifidobacteria typically represent the most abundant bacteria of the human gut microbiota in healthy breast-fed infants. Members of the Bifidobacterium bifidum species constitute one of the dominant taxa amongst these bifidobacterial communities and have been shown to display notable physiological and genetic features encompassing adhesion to epithelia as well as metabolism of host-derived glycans. In the current review, we discuss current knowledge concerning particular biological characteristics of the B. bifidum species that support its specific adaptation to the human gut and their implications in terms of supporting host health. Full article
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