Comparative Genomics of the Human Gut Microbiome

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 19385

Special Issue Editors

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
University College Cork, APC Microbiome Ireland, Cork, Ireland
Interests: gut microbiota; comparative genomics; bacteriophages; phage evolution and ecology
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

Special Issue Information

Dear Colleagues,

The gastrointestinal tract harbours a complex ecological community, playing an important role in human nutrition and health. The gut microbiota is a dynamically evolving ecosystem composed of a wide variety of microbes (e.g., bacteria, archaea, eukarya and viruses), taking part in the host physiology and metabolism. In particular, fermentation of dietary components that escape gut digestion, stimulation of the host immune systems, defence against infections combined with the conversion of bioactive compounds and biosynthesis of secondary metabolites represent key microbial functions of the gut ecosystem. Perturbation of this delicate balance may have serious implications for host health and functionality. It is now understood that several factors such as host genetics, diet and use of medications play a role in influencing the composition of the gut communities. However, more recent advances in the study of gut viromes have also brought attention to the aspect of phage–host coevolution and predatory dynamics as another important modulator of the gut bacterial composition. In the study of the human gut microbiome, culture-independent sequencing approaches, including metagenomics and comparative genomics, continue to provide important insights into the existing dynamics influencing the diversity of the gut populations.   

This Special Issue aims to gather the latest advances in the application of comparative and functional genomics and metagenomics methods in the study of the human gut ecosystem. We would like to invite researchers to submit their research or review articles showing the application of such methods in the study of bacterial and virome communities, in unravelling bacterial–host interactions, new therapies and new molecular pathways.

Dr. Francesca Bottacini
Dr. Colin Buttimer
Dr. Jennifer Mahony
Prof. Dr. Douwe van Sinderen
Guest Editors

Manuscript Submission Information

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Keywords

  • Gut microbiota 
  • Comparative genomics 
  • Functional genomics 
  • Metagenomics 
  • Virome 
  • Microbiome 
  • Gut health 
  • Functional foods

Published Papers (5 papers)

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Research

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17 pages, 1268 KiB  
Article
Comparative Genomics and Physiology of Akkermansia muciniphila Isolates from Human Intestine Reveal Specialized Mucosal Adaptation
by Janneke P. Ouwerkerk, Hanne L. P. Tytgat, Janneke Elzinga, Jasper Koehorst, Pieter Van den Abbeele, Bernard Henrissat, Miguel Gueimonde, Patrice D. Cani, Tom Van de Wiele, Clara Belzer and Willem M. de Vos
Microorganisms 2022, 10(8), 1605; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10081605 - 09 Aug 2022
Cited by 5 | Viewed by 3300
Abstract
Akkermansia muciniphila is a champion of mucin degradation in the human gastrointestinal tract. Here, we report the isolation of six novel strains from healthy human donors and their genomic, proteomic and physiological characterization in comparison to the type-strains A. muciniphila MucT and [...] Read more.
Akkermansia muciniphila is a champion of mucin degradation in the human gastrointestinal tract. Here, we report the isolation of six novel strains from healthy human donors and their genomic, proteomic and physiological characterization in comparison to the type-strains A. muciniphila MucT and A. glycaniphila PytT. Complete genome sequencing revealed that, despite their large genomic similarity (>97.6%), the novel isolates clustered into two distinct subspecies of A. muciniphila: Amuc1, which includes the type-strain MucT, and AmucU, a cluster of unassigned strains that have not yet been well characterized. CRISPR analysis showed all strains to be unique and confirmed that single healthy subjects can carry more than one A. muciniphila strain. Mucin degradation pathways were strongly conserved amongst all isolates, illustrating the exemplary niche adaptation of A. muciniphila to the mucin interface. This was confirmed by analysis of the predicted glycoside hydrolase profiles and supported by comparing the proteomes of A. muciniphila strain H2, belonging to the AmucU cluster, to MucT and A. glycaniphila PytT (including 610 and 727 proteins, respectively). While some intrinsic resistance was observed among the A. muciniphila straind, none of these seem to pose strain-specific risks in terms of their antibiotic resistance patterns nor a significant risk for the horizontal transfer of antibiotic resistance determinants, opening the way to apply the type-strain MucT or these new A. muciniphila strains as next generation beneficial microbes. Full article
(This article belongs to the Special Issue Comparative Genomics of the Human Gut Microbiome)
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17 pages, 1925 KiB  
Article
In Vitro and In Silico Based Approaches to Identify Potential Novel Bacteriocins from the Athlete Gut Microbiome of an Elite Athlete Cohort
by Laura Wosinska, Calum J. Walsh, Paula M. O’Connor, Elaine M. Lawton, Paul D. Cotter, Caitriona M. Guinane and Orla O’Sullivan
Microorganisms 2022, 10(4), 701; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10040701 - 24 Mar 2022
Cited by 8 | Viewed by 3499
Abstract
Exercise reduces inflammation, fatigue, and aids overall health. Additionally, physical fitness has been associated with desirable changes in the community composition of the athlete gut microbiome, with health-associated taxa being shown to be increased in active individuals. Here, using a combination of in [...] Read more.
Exercise reduces inflammation, fatigue, and aids overall health. Additionally, physical fitness has been associated with desirable changes in the community composition of the athlete gut microbiome, with health-associated taxa being shown to be increased in active individuals. Here, using a combination of in silico and in vitro methods, we investigate the antimicrobial activity of the athlete gut microbiome. In vitro approaches resulted in the generation of 284 gut isolates with inhibitory activity against Clostridioides difficile and/or Fusobacterium nucleatum, and the most potent isolates were further characterized, and potential bacteriocins were predicted using both MALDI-TOF MS and whole-genome sequencing. Additionally, metagenomic reads from the faecal samples were used to recover 770 Metagenome Assembled Genomes (MAGs), of which 148 were assigned to be high-quality MAGs and screened for the presence of putative bacteriocin gene clusters using BAGEL4 software, with 339 gene clusters of interest being identified. Class I was the most abundant bacteriocin class predicted, accounting for 91.3% of predictions, Class III had a predicted abundance of 7.5%, and Class II was represented by just 1% of all predictions. Full article
(This article belongs to the Special Issue Comparative Genomics of the Human Gut Microbiome)
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25 pages, 6195 KiB  
Article
Selective Isolation of Eggerthella lenta from Human Faeces and Characterisation of the Species Prophage Diversity
by Colin Buttimer, Francesca Bottacini, Andrey N. Shkoporov, Lorraine A. Draper, Paul Ross and Colin Hill
Microorganisms 2022, 10(1), 195; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010195 - 17 Jan 2022
Cited by 6 | Viewed by 3965
Abstract
Eggerthella lenta is an anaerobic, high GC, Gram-positive bacillus commonly found in the human digestive tract that belongs to the class Coriobacteriia of the phylum Actinobacteria. This species has been of increasing interest as an important player in the metabolism of xenobiotics and [...] Read more.
Eggerthella lenta is an anaerobic, high GC, Gram-positive bacillus commonly found in the human digestive tract that belongs to the class Coriobacteriia of the phylum Actinobacteria. This species has been of increasing interest as an important player in the metabolism of xenobiotics and dietary compounds. However, little is known regarding its susceptibility to bacteriophage predation and how this may influence its fitness. Here, we report the isolation of seven novel E. lenta strains using cefotaxime and ceftriaxone as selective agents. We conducted comparative and pangenome analyses of these strains and those publicly available to investigate the diversity of prophages associated with this species. Prophage gene products represent a minimum of 5.8% of the E. lenta pangenome, comprising at least ten distantly related prophage clades that display limited homology to currently known bacteriophages. All clades possess genes implicated in virion structure, lysis, lysogeny and, to a limited extent, DNA replication. Some prophages utilise tyrosine recombinases and diversity generating retroelements to generate phase variation among targeted genes. The prophages have differing levels of sensitivity to the CRISPR/cas systems of their hosts, with spacers from 44 E. lenta isolates found to target only five out of the ten identified prophage clades. Furthermore, using a PCR-based approach targeting the prophage attP site, we were able to determine that several of these elements can excise from the host chromosome, thus supporting the notion that these are active prophages. The findings of this study provide further insights into the diversity of prophages infecting species of the phylum Actinobacteria. Full article
(This article belongs to the Special Issue Comparative Genomics of the Human Gut Microbiome)
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16 pages, 4364 KiB  
Article
Diversity of Human-Associated Bifidobacterial Prophage Sequences
by Darren Buckley, Toshitaka Odamaki, Jinzhong Xiao, Jennifer Mahony, Douwe van Sinderen and Francesca Bottacini
Microorganisms 2021, 9(12), 2559; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9122559 - 10 Dec 2021
Cited by 4 | Viewed by 2452
Abstract
Members of Bifidobacterium play an important role in the development of the immature gut and are associated with positive long-term health outcomes for their human host. It has previously been shown that intestinal bacteriophages are detected within hours of birth, and that induced [...] Read more.
Members of Bifidobacterium play an important role in the development of the immature gut and are associated with positive long-term health outcomes for their human host. It has previously been shown that intestinal bacteriophages are detected within hours of birth, and that induced prophages constitute a significant source of such gut phages. The gut phageome can be vertically transmitted from mother to newborn and is believed to exert considerable selective pressure on target prokaryotic hosts affecting abundance levels, microbiota composition, and host characteristics. The objective of the current study was to investigate prophage-like elements and predicted CRISPR-Cas viral immune systems present in publicly available, human-associated Bifidobacterium genomes. Analysis of 585 fully sequenced bifidobacterial genomes identified 480 prophage-like elements with an occurrence of 0.82 prophages per genome. Interestingly, we also detected the presence of very similar bifidobacterial prophages and corresponding CRISPR spacers across different strains and species, thus providing an initial exploration of the human-associated bifidobacterial phageome. Our analyses show that closely related and likely functional prophages are commonly present across four different species of human-associated Bifidobacterium. Further comparative analysis of the CRISPR-Cas spacer arrays against the predicted prophages provided evidence of historical interactions between prophages and different strains at an intra- and inter-species level. Clear evidence of CRISPR-Cas acquired immunity against infection by bifidobacterial prophages across several bifidobacterial strains and species was obtained. Notably, a spacer representing a putative major capsid head protein was found on different genomes representing multiple strains across B. adolescentis, B. breve, and B. bifidum, suggesting that this gene is a preferred target to provide bifidobacterial phage immunity. Full article
(This article belongs to the Special Issue Comparative Genomics of the Human Gut Microbiome)
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Review

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15 pages, 1456 KiB  
Review
Biases in Viral Metagenomics-Based Detection, Cataloguing and Quantification of Bacteriophage Genomes in Human Faeces, a Review
by Julie Callanan, Stephen R. Stockdale, Andrey Shkoporov, Lorraine A. Draper, R. Paul Ross and Colin Hill
Microorganisms 2021, 9(3), 524; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9030524 - 04 Mar 2021
Cited by 16 | Viewed by 4389
Abstract
The human gut is colonised by a vast array of microbes that include bacteria, viruses, fungi, and archaea. While interest in these microbial entities has largely focused on the bacterial constituents, recently the viral component has attracted more attention. Metagenomic advances, compared to [...] Read more.
The human gut is colonised by a vast array of microbes that include bacteria, viruses, fungi, and archaea. While interest in these microbial entities has largely focused on the bacterial constituents, recently the viral component has attracted more attention. Metagenomic advances, compared to classical isolation procedures, have greatly enhanced our understanding of the composition, diversity, and function of viruses in the human microbiome (virome). We highlight that viral extraction methodologies are crucial in terms of identifying and characterising communities of viruses infecting eukaryotes and bacteria. Different viral extraction protocols, including those used in some of the most significant human virome publications to date, have introduced biases affecting their a overall conclusions. It is important that protocol variations should be clearly highlighted across studies, with the ultimate goal of identifying and acknowledging biases associated with different protocols and, perhaps, the generation of an unbiased and standardised method for examining this portion of the human microbiome. Full article
(This article belongs to the Special Issue Comparative Genomics of the Human Gut Microbiome)
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