Exploring the role of the microbiota member <i>Bifidobacterium</i> in modulating immune-linked diseases

O’Neill, Ian; Schofield, Zoe; Hall, Lindsay J.

doi:10.1042/etls20170058

Cited by 93 publications

(68 citation statements)

References 106 publications

(115 reference statements)

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“…Our previous studies demonstrated an important role for infant-associated Bifidobacterium breve, which reduced pathological cell shedding processes in adult mice via the bifidobacterial exopolysaccharide capsule and host MyD88 signalling interactions [16,28]. Although Bifidobacterium is found at high levels in infants, species and strains of this genus are not consistently detected in neonatal mice.…”

Section: Discussionmentioning

confidence: 99%

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

Hughes

Schofield

Dalby

et al. 2019

Preprint

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AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of 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, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, 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. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

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Section: Discussionmentioning

confidence: 99%

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

Hughes

Schofield

Dalby

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Our previous studies demonstrated an important role for infant‐associated Bifidobacterium breve, which reduced pathological cell shedding processes in adult mice via the bifidobacterial exopolysaccharide capsule and host MyD88 signaling interactions 17,35 . Although Bifidobacterium is found at high levels in infants, species and strains of this genus are not consistently detected in neonatal mice.…”

Section: Discussionmentioning

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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“…The early-life developmental window represents a critical time for microbe-host interactions as this is when foundations for future health and well-being are established. Colonisation of pioneer microbes shortly after birth represents a key first step in this mutualistic relationship; shaping the developing microbial community, and in turn impacting numerous host physiological processes [1][2][3][4][5]. Although the microbiota of adults is complex in nature, the gastrointestinal (GI) tract of full-term healthy infants is relatively simplistic, dominated by the genus Bifidobacterium that can persist into early childhood [3,6].…”

Section: Introductionmentioning

confidence: 99%

“…Although the microbiota of adults is complex in nature, the gastrointestinal (GI) tract of full-term healthy infants is relatively simplistic, dominated by the genus Bifidobacterium that can persist into early childhood [3,6]. In the first months of birth, the loss of Bifidobacterium species or gain of other bacteria during this critical window of opportunity, may significantly alter the 'natural' progression of the microbial community that may lead to a variety of negative consequences for host health including a predisposition to autoimmune/metabolic diseases (like allergies and childhood obesity) [1,2].…”

Section: Introductionmentioning

confidence: 99%

Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem

et al. 2019

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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 1 H-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.

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Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

Cited by 93 publications

References 106 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

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

Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem

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