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Tims, S.

Publications and source records attributed to Tims, S..

3 recordsLinked to original sources

Grain versus AIN: Common rodent diets differentially affect breeding and metabolic health outcomes in adult C57BL/6j mice

Semi-synthetic and grain-based diets are common rodent diets for biomedical research. Both diet types are considered nutritionally adequate to support breeding, growth, and long life, yet there are fundamental differences between them that may affect metabolic processes. We have characterized the effects of diet type on breeding outcomes, metabolic phenotype, and microbiota profile in adult mice. Healthy 8-week-old female and male C57BL/6J mice were fed a semi-synthetic or a grain-based diet for 12 weeks and changes in body weight and body composition were monitored. Breeding outcomes were determined. Body fat accumulation of female mice was lower on the semi-synthetic diet than on the grain-based diet. Pregnancy rate and newborn pup survival appeared to be lower in mice exposed to semi-synthetic diet compared to grain-based diet. Both female and male mice showed a profound change in fecal microbiota alpha and beta diversity depending on diet type. Our study shows that type of rodent diet may affect breeding outcomes whilst influencing metabolism and health of female laboratory mice. These factors have the potential to influence other experimental outcomes and the results suggest that semi-synthetic and grain-based diets are not interchangeable in research using rodent models. Careful consideration and increased understanding of the consequences of diet choice would lead to improvements in experimental design and reproducibility of study results.

physiology↗

The role of the gut microbiota in the effects of early-life stress and dietary fatty acids on later-life central and metabolic outcomes in mice

Early-life stress (ELS) leads to increased vulnerability for mental and metabolic disorders. We have previously shown that dietary low {omega}-6/{omega}-3 polyunsaturated fatty acid (PUFA) ratio is able to protect against ELS-induced cognitive impairments. Due to the importance of the gut microbiota as determinants of long-term health, we here study the impact of ELS and dietary PUFAs on the gut microbiota, and how this relates to the previously described cognitive, metabolic and fatty acid profiles. Male mice were exposed to ELS via the limited bedding and nesting paradigm (postnatal day (P)2 - P9) and to an early diet (P2 - P42) with either high (15) or low (1) {omega}-6 linoleic acid to {omega}-3 alpha-linolenic acid ratio. 16S ribosomal RNA was sequenced and analyzed from fecal samples at P21, P42 and P180. ELS increased {beta}-diversity at P42, which persisted into adulthood. The low {omega}-6/{omega}-3 diet prevented the ELS-induced increase in {beta}-diversity, at P42. At the level of taxa abundance, for example, the abundance of the phyla Bacteroidetes increased while Actinobacteria and Verrucomicrobia decreased with age; ELS reduced the relative abundance of the genera RC9 gut group and Rikenella into adulthood and the low {omega}-6/{omega}-3 diet reduced the abundance of the Firmicutes Erysipelotrichia. At P42, species abundance correlated with body fat mass and circulating leptin (e.g. Bacteroidetes and Proteobacteria taxa) and fatty acid profiles (e.g. Firmicutes taxa). This study gives novel insights into the impact of age, ELS and dietary PUFAs on microbiota composition, providing potential targets for non-invasive (nutritional) modulation of the ELS-induced deficits. ImportanceEarly-life stress (ELS) leads to increased vulnerability to develop mental and metabolic disorders, however the biological mechanisms leading to such programming are not fully clear. Increased attention has been given to the importance of the gut microbiota as determinant of long term health and as potential target for non-invasive nutritional strategies to protect against the negative impact of ELS. Here we give novel insights in the complex interaction between ELS, early dietary {omega}-3 availability and the gut microbiota across ages and provides new potential targets for (nutritional) modulation of the long-term effects of the early-life environment via the microbiota.

microbiology↗

Cross-feeding between Bifidobacterium infantis and Anaerostipes caccae on lactose and human milk oligosaccharides

The establishment of the gut microbiota immediately after birth is a dynamic process that may impact lifelong health. At this important developmental stage in early life, human milk oligosaccharides (HMOS) serve as specific substrates to promote the growth of gut microbes, particularly the group of Actinobacteria (bifidobacteria). Later in life, this shifts to the colonisation of Firmicutes and Bacteroidetes, which generally dominate the human gut throughout adulthood. The well-orchestrated transition is important for health, as an aberrant microbial composition and/or SCFA production are associated with colicky symptoms and atopic diseases in infants. Here, we study the trophic interactions between an HMOS-degrader, Bifidobacterium longum subsp. infantis and the butyrogenic Anaerostipes caccae using carbohydrate substrates that are relevant in this early life period, i.e. lactose and HMOS. Mono-and co-cultures of these bacterial species were grown at pH 6.5 in anaerobic bioreactors supplemented with lactose or total human milk carbohydrates (containing both lactose and HMOS). A cac was not able to grow on these substrates except when grown in co-culture with B. inf, leading concomitant butyrate production. Cross-feeding was observed, in which A. cac utilised the liberated monosaccharides as well as lactate and acetate produced by B. inf. This microbial cross-feeding is indicative of the key ecological role of bifidobacteria in providing substrates for other important species to colonise the infant gut. The symbiotic relationship between these key species contributes to the gradual production of butyrate early in life that could be important for host-microbial cross-talk and gut maturation.\n\nImportanceThe establishment of a healthy infant gut microbiota is crucial for the immune, metabolic and neurological development of infants. Recent evidence suggests that an aberrant gut microbiota early in life could lead to discomfort and predispose infants to the development of immune related diseases. This paper addresses the ecosystem function of two resident microbes of the infant gut. The significance of this research is the proof of cross-feeding interactions between HMOS-degrading bifidobacteria and a butyrate-producing microorganism. Bifidobacteria in the infant gut that support the growth and butyrogenesis of butyrate-producing bacteria, could orchestrated an important event of maturation for both the gut ecosystem and physiology of infant.

microbiology↗