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1.
Microbiol Resour Announc ; 12(11): e0041223, 2023 Nov 16.
Article En | MEDLINE | ID: mdl-37815360

Here, we describe the draft genome sequence of Bifidobacterium breve DSM 32583 isolated from human milk obtained from a healthy mother. Potentially, this B. breve strain could serve as a probiotic.

2.
Nat Commun ; 14(1): 1349, 2023 03 11.
Article En | MEDLINE | ID: mdl-36906612

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.


Gastrointestinal Microbiome , Infant, Premature , Infant , Infant, Newborn , Humans , Female , RNA, Ribosomal, 16S/genetics , Ecosystem , Intestines , Feces/microbiology , Bifidobacterium longum subspecies infantis/genetics
3.
Anaerobe ; 80: 102713, 2023 Apr.
Article En | MEDLINE | ID: mdl-36754140

Prophylactic administration of oral probiotics is associated with significant reductions in the morbidity and mortality of necrotising enterocolitis in preterm infants. We document the first case of Bifidobacterium longum subsp. infantis sub-clinical bacteraemia, in an extremely low birth weight preterm infant, since introduction of routine probiotic treatment at the Norfolk and Norwich University Hospital 10 years ago. Whole genome comparisons confirmed the isolated strain likely originated from the probiotic product.


Bacteremia , Probiotics , Infant , Infant, Newborn , Humans , Infant, Premature , Bifidobacterium/genetics , Bacteremia/diagnosis , Bifidobacterium longum subspecies infantis
4.
ISME Commun ; 2(1): 20, 2022 Feb 25.
Article En | MEDLINE | ID: mdl-37938745

Members of the gut microbiota genus Bifidobacterium are widely distributed human and animal symbionts believed to exert beneficial effects on their hosts. However, in-depth genomic analyses of animal-associated species and strains are somewhat lacking, particularly in wild animal populations. Here, to examine patterns of host specificity and carbohydrate metabolism capacity, we sequenced whole genomes of Bifidobacterium isolated from wild-caught small mammals from two European countries (UK and Lithuania). Members of Bifidobacterium castoris, Bifidobacterium animalis and Bifodobacterium pseudolongum were detected in wild mice (Apodemus sylvaticus, Apodemus agrarius and Apodemus flavicollis), but not voles or shrews. B. castoris constituted the most commonly recovered Bifidobacterium (78% of all isolates), with the majority of strains only detected in a single population, although populations frequently harboured multiple co-circulating strains. Phylogenetic analysis revealed that the mouse-associated B. castoris clades were not specific to a particular location or host species, and their distribution across the host phylogeny was consistent with regular host shifts rather than host-microbe codiversification. Functional analysis, including in vitro growth assays, suggested that mouse-derived B. castoris strains encoded an extensive arsenal of carbohydrate-active enzymes, including putative novel glycosyl hydrolases such as chitosanases, along with genes encoding putative exopolysaccharides, some of which may have been acquired via horizontal gene transfer. Overall, these results provide a rare genome-level analysis of host specificity and genomic capacity among important gut symbionts of wild animals, and reveal that Bifidobacterium has a labile relationship with its host over evolutionary time scales.

6.
Cell Rep Med ; 1(5): 100077, 2020 08 25.
Article En | MEDLINE | ID: mdl-32904427

Supplementation with members of the early-life microbiota as "probiotics" is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium-dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.


Bifidobacterium/physiology , Gastrointestinal Microbiome/physiology , Infant, Premature/metabolism , Infant, Premature/physiology , Lactobacillus/physiology , Metabolome/physiology , Bifidobacterium/genetics , Breast Feeding/methods , Dietary Supplements/microbiology , Feces/microbiology , Gastrointestinal Microbiome/genetics , Humans , Infant , Infant, Newborn , Lactobacillus/genetics , Longitudinal Studies , Milk, Human/microbiology , Probiotics/administration & dosage , RNA, Ribosomal, 16S/genetics
7.
iScience ; 23(8): 101368, 2020 Aug 21.
Article En | MEDLINE | ID: mdl-32721872

Diet-microbe interactions play a crucial role in modulation of the early life microbiota and infant health. Bifidobacterium dominates the breast-fed infant gut and may persist in individuals during transition from a milk-based to a more diversified diet. Here, we investigated adaptation of Bifidobacterium longum to the changing nutritional environment. Genomic characterization of 75 strains isolated from nine either exclusively breast- or formula-fed (pre-weaning) infants in their first 18 months revealed subspecies- and strain-specific intra-individual genomic diversity with respect to carbohydrate metabolism, which corresponded to different dietary stages. Complementary phenotypic studies indicated strain-specific differences in utilization of human milk oligosaccharides and plant carbohydrates, whereas proteomic profiling identified gene clusters involved in metabolism of selected carbohydrates. Our results indicate a strong link between infant diet and B. longum diversity and provide additional insights into possible competitive advantage mechanisms of this Bifidobacterium species and its persistence in a single host.

8.
Nat Microbiol ; 5(3): 430-442, 2020 03.
Article En | MEDLINE | ID: mdl-31844297

The MinION sequencing platform offers near real-time analysis of DNA sequence; this makes the tool attractive for deployment in fieldwork or clinical settings. We used the MinION platform coupled to the NanoOK RT software package to perform shotgun metagenomic sequencing and profile mock communities and faecal samples from healthy and ill preterm infants. Using Nanopore data, we reliably classified a 20-species mock community and captured the diversity of the immature gut microbiota over time and in response to interventions such as probiotic supplementation, antibiotic treatment or episodes of suspected sepsis. We also performed rapid real-time runs to assess gut-associated microbial communities in critically ill and healthy infants, facilitated by NanoOK RT software package, which analysed sequences as they were generated. Our pipeline reliably identified pathogenic bacteria (that is, Klebsiella pneumoniae and Enterobacter cloacae) and their corresponding antimicrobial resistance gene profiles within as little as 1 h of sequencing. Results were confirmed using pathogen isolation, whole-genome sequencing and antibiotic susceptibility testing, as well as mock communities and clinical samples with known antimicrobial resistance genes. Our results demonstrate that MinION (including cost-effective Flongle flow cells) with NanoOK RT can process metagenomic samples to a rich dataset in < 5 h, which creates a platform for future studies aimed at developing these tools and approaches in clinical settings with a focus on providing tailored patient antimicrobial treatment options.


Drug Resistance, Bacterial/drug effects , Drug Resistance, Bacterial/genetics , Infant, Premature , Microbiota/drug effects , Microbiota/genetics , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/genetics , Computational Biology , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Enterobacter cloacae/drug effects , Enterobacter cloacae/genetics , Enterobacter cloacae/isolation & purification , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/isolation & purification , Metagenome , Microbial Sensitivity Tests , Nanopores , Sequence Analysis, DNA , Software , Whole Genome Sequencing
9.
ISME J ; 14(2): 635-648, 2020 02.
Article En | MEDLINE | ID: mdl-31740752

Diet-microbe interactions play an important role in modulating the early-life microbiota, with Bifidobacterium strains and species dominating the gut of breast-fed infants. Here, we sought to explore how infant diet drives distinct bifidobacterial community composition and dynamics within individual infant ecosystems. Genomic characterisation of 19 strains isolated from breast-fed infants revealed a diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct to each strain, but collectively formed a pangenome across infants. Presence of gene clusters implicated in digestion of human milk oligosaccharides (HMOs) varied between species, with growth studies indicating that within single infants there were differences in the ability to utilise 2'FL and LNnT HMOs between strains. Cross-feeding experiments were performed with HMO degraders and non-HMO users (using spent or 'conditioned' media and direct co-culture). Further 1H-NMR analysis identified fucose, galactose, acetate, and N-acetylglucosamine as key by-products of HMO metabolism; as demonstrated by modest growth of non-HMO users on spend media from HMO metabolism. These experiments indicate how HMO metabolism permits the sharing of resources to maximise nutrient consumption from the diet and highlights the cooperative nature of bifidobacterial strains and their role as 'foundation' species in the infant ecosystem. The intra- and inter-infant bifidobacterial community behaviour may contribute to the diversity and dominance of Bifidobacterium in early life and suggests avenues for future development of new diet and microbiota-based therapies to promote infant health.


Bifidobacterium , Carbohydrate Metabolism/genetics , Milk, Human , Oligosaccharides/genetics , Bifidobacterium/genetics , Bifidobacterium/isolation & purification , Bifidobacterium/physiology , Breast Feeding , Ecosystem , Female , Genes, Bacterial , Genetic Variation , Genome, Bacterial , Humans , Infant , Metagenome/genetics , Metagenome/physiology , Microbial Interactions , Microbiota , Milk, Human/chemistry , Oligosaccharides/metabolism
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