Biology subjects

Chalklen, L.

Publications and source records attributed to Chalklen, L..

4 recordsLinked to original sources

bioRxiv2025

Host-specific microbiome and genomic signatures in Bifidobacterium reveal co-evolutionary and functional adaptations across diverse animal hosts

Animal hosts harbour divergent microbiota, including various Bifidobacterium species and strains, yet their evolutionary relationships, and functional adaptions remain understudied. By integrating taxonomic, genomic and predicted functional annotations, we uncover how Bifidobacterium adapts to host-specific environments, shaped by vertical transmission, dietary influences, and host phylogeny. Our findings reveal that host phylogeny is a major determinant of gut microbiota composition. Distinct microbial networks in mammalian and avian hosts reflect evolutionary adaptations to dietary niches, such as carnivory, and ecological pressures. At a strain-resolved level, we identify strong co-phylogenetic associations between Bifidobacterium strains and their hosts, driven by vertical transmission and dietary selection, underscoring the intricate co-evolutionary dynamics between these microbes and their hosts. Functional analyses highlight striking host-specific metabolic adaptations in Bifidobacterium, particularly in carbohydrate metabolism and oxidative stress responses. In mammals, we observe an enrichment of glycoside hydrolases (GH) tailored to complex carbohydrate-rich diets, including multi-domain GH13_28 -amylases featuring diverse carbohydrate-binding modules (CBM25, CBM26, and the novel CBM74). These adaptations emphasise the ecological flexibility of Bifidobacterium in breaking down -linked glucose polysaccharides, such as resistant starch. Together, our study provides new insights into the evolutionary trajectories and ecological plasticity of Bifidobacterium, revealing how host phylogeny and dietary ecology drive microbial diversity and function. These findings deepen our understanding of host-microbe co-evolution and the critical role of microbiota in shaping animal health and adaptation.

microbiology↗

bioRxiv2019

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

The 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.

microbiology↗

bioRxiv2019

Infant diet promotes Bifidobacterium community cooperation within a single ecosystem

Diet-microbe interactions play an important role in modulating the early life microbiota, with Bifidobacterium strains and species dominating the gut microbiota 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 within infant differences in the ability to utilise 2FL and LNnT HMOs between strains. We also performed cross-feeding experiments using metabolic products from growth on 2FL or LNnT for non-HMO degrading isolates, these compounds were identified to include fucose, galactose, acetate and N-acetylglucosamine. These data highlight the cooperative nature of individual bifidobacterial founder strains within an infant ecosystem, and how sharing resources maximises nutrient consumption from the diet. We propose that this social behaviour contributes to the diversity and dominance of Bifidobacterium in early life and suggests avenues for development of new diet and microbiota based therapies to promote infant health.

microbiology↗

bioRxiv2019

Microbiota supplementation with Bifidobacterium and Lactobacillus modifies the preterm infant gut microbiota and metabolome

Supplementation with members of the early-life microbiota or probiotics is becoming increasingly popular to attempt to beneficially manipulate the preterm gut microbiota. We performed a large longitudinal study comprising two preterm groups; 101 orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 non-supplemented (Control) matched by age, sex, birth-mode, and diet. 16S rRNA metataxonomic profiling on stool samples (n = 592) indicated a predominance of Bifidobacterium, and a reduction of pathobionts in the Bif/Lacto group. Metabolic phenotyping found a parallel increase in fecal acetate and lactate in the Bif/Lacto group compared to the Control group, which positively correlated with Bifidobacterium abundance consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides and reduced gut pH. This study demonstrates that microbiota supplementation can modify the preterm microbiome and the gastrointestinal environment to more closely resemble that of a full-term infant.

microbiology↗