Microbiota supplementation with<i>Bifidobacterium</i>and<i>Lactobacillus</i>modifies the preterm infant gut microbiota and metabolome

Alcon-Giner, Cristina; Dalby, Matthew J.; Caim, Shabhonam; Ketskemety, Jennifer; Shaw, Alexander; Sim, Kathleen; Lawson, Melissa A.; Kiu, Raymond; Leclaire, Charlotte; Chalklen, Lisa; Kujawska, Magdalena; Fardus‐Reid, Fahmina; Belteki, Gusztav; Lloyd, Katherine; Swann, Jonathan R.; Kroll, J. Simon; Clarke, Paul; Hall, Lindsay J.

doi:10.1101/698092

Cited by 14 publications

(16 citation statements)

References 69 publications

(82 reference statements)

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“…Reads that passed threshold were aligned against SILVA database (version: SILVA_132_SSURef_tax_silva) using BLASTN (ncbi‐blast‐2.2.25+; Max e‐value 10e−3) separately for both pairs. After performing BLASTN alignment, all output files were imported and annotated using the paired‐end protocol of MEGAN on default Lowest Common Ancestor (LCA) parameters 24 . For analysis of microbiota composition, the samples were normalized by subsampling each sample to 3224 reads (the number of reads of the lowest sample) to equalize library sizes using the Phyloseq package version 1.24.2 in RStudio version 1.1.463.…”

Section: Methodsmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

et al. 2020

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The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect.Our findings further support the importance of the early life window for microbiotaepithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation. K E Y W O R D S antibiotics, cell shedding, early life, fecal microbiota transplant, inflammation, intestinal epithelium, metabolites, microbiota 7076 | HUGHES Et al.

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Section: Methodsmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

et al. 2020

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“…Genomic DNA extraction of mouse caecal samples on day 4 was performed with FastDNA Spin Kit for Soil following manufacturer’s instructions and extending the bead-beating step to 3 min as described previously [56]. Extracted DNA was quantified, normalised and sequenced on Illumina MiSeq platform using a read length of 2 × 300 bp, sequencing reads were analysed using OTU clustering methods (QIIME v1.9.1) to assign bacterial taxonomy and visualised as described previously [57, 58].…”

Section: Methodsmentioning

confidence: 99%

Bifidobacterium breveUCC2003 induces a distinct global transcriptomic programme in neonatal murine intestinal epithelial cells

Kiu¹,

Treveil

Harnisch³

et al. 2020

Preprint

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SummaryBifidobacterium is an important gut microbiota member during early life that is associated with improved gut health. However, the underlying health-driving mechanisms are not well understood, particularly how Bifidobacterium may modulate the intestinal barrier via programming of intestinal epithelial cells (IECs). In this study, we sought to investigate the global impact of model strain Bifidobacterium breve UCC2003 on the neonatal IEC transcriptome, including gene regulation and pathway modulation. Small IECs from two-week-old neonatal mice administered B. breve UCC2003 for three consecutive days or PBS (control group) were subjected to global RNASeq, with various bioinformatic approaches used to determine differentially expressed genes, pathways and affected cell types between control and experimental groups. Whilst colonisation with B. breve had minimal impacts on the neonatal microbiota, we observed extensive regulation of the IEC transcriptome; ~4,000 genes significantly up-regulated, including key genes associated with epithelial barrier function. Enrichment of cell differentiation and cell proliferation pathways were observed, along with an overrepresentation of stem cell marker genes, indicating an increase in the regenerative potential of the epithelial layer. Expression of distinct immune-associated pathway members (e.g. Toll-like Receptors) were also affected after neonatal B. breve colonisation. In conclusion, B. breve UCC2003 plays a central role in driving universal transcriptomic changes in neonatal IECs that enhances cell replication, differentiation and growth, predominantly in the stem cell compartment. This study enhances our overall understanding of the benefits of B. breve in driving intestinal epithelium homeostatic development during early life, with potential avenues to develop novel live biotherapeutic products.

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“…DNA was extracted from samples using the FastDNA SPIN Kit for Soil (MP Biomedicals) and processed for sequencing and analyses as described previously [16]. This 16S rRNA gene sequence data associated with this project have been deposited at DDBJ/ENA/GenBank under BioProject accession PRJEB34372.…”

Section: Methodsmentioning

confidence: 99%

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

Chen

Brook

Soe

et al. 2019

Preprint

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Klebsiella spp. are frequently enriched in the gut microbiota of preterm neonates, and overgrowth is associated with necrotizing enterocolitis, nosocomial infections and late-onset sepsis. Little is known about the genomic and phenotypic characteristics of preterm-associated Klebsiella as previous studies have focussed on recovery of antimicrobial-resistant isolates or culture-independent molecular analyses. Faecal samples from a UK cohort of healthy and sick preterm neonates (n=109) were screened on MacConkey agar to isolate lactose-positive Enterobacteriaceae. Whole-genome sequences were generated for isolates. Approximately one-tenth of faecal samples harboured Klebsiella spp. (Klebsiella pneumoniae, 7.3 %; Klebsiella quasipneumoniae, 0.9 %; Klebsiella grimontii, 2.8 %; Klebsiella michiganensis, 1.8 %). Isolates recovered from NEC- and sepsis-affected infants and those showing no signs of clinical infection (i.e. ‘healthy’) encoded multiple β-lactamases, which may prove problematic when defining treatment regimens for NEC or sepsis, and suggest ‘healthy’ preterm infants contribute to the resistome. No difference was observed between isolates recovered from ‘healthy’ and sick infants with respect to in vitro siderophore production (all encoded enterobactin in their genomes). All K. pneumoniae, K. quasipneumoniae, K. grimontii and K. michiganensis faecal isolates tested were able to reside and persist in macrophages, indicating their immune evasion abilities. Using a curated dataset of Klebsiella oxytoca, K. grimontii and K. michiganensis whole-genome sequences, metapangenome analyses of published metagenomic data confirmed our findings regarding the presence of K. michiganensis in the preterm gut, and highlight the importance of refined analyses with curated sequence databases when studying closely related species present in metagenomic data.

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Microbiota supplementation withBifidobacteriumandLactobacillusmodifies the preterm infant gut microbiota and metabolome

Cited by 14 publications

References 69 publications

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Bifidobacterium breveUCC2003 induces a distinct global transcriptomic programme in neonatal murine intestinal epithelial cells

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

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