Project description:A whole-food, plant-based diet rich in fruits and vegetables in addition to whole grains and legumes is highly praised for its positive health benefits. A reason for that is the high content of dietary fibres that are essential for optimal health and well-being. However, most people in the UK do not meet the minimum daily intake of at least 30 g. Gum Arabic (GA), a safe and rich source of soluble fibre, could potentially be incorporated into a typical Western diet as more evidence-based research confers its positive impact on health. To elucidate the mechanisms of action of GA’s role in health improvement, we combined bioinformatics (RNA-seq and 16S rRNA microbiome analysis) with metabolomics in combination with the zebrafish (Danio rerio) model. The results of this study show that a two-week diet consisting of 60% GA can significantly (adjusted p-value < 0.05) alter the expression levels of three genes related to appetite control and neuroprotection in the zebrafish brain. Our analysis also shows that incorporating GA into the diet affects the structure of the microbiota. It induces a variation in richness and bacterial taxa abundance by reducing microbiome alpha diversity and increasing the similarity in the microbial structure of the treated samples which is suggestive of a possible strain-specific selectivity mechanism. Overall, the significance of this report lies in its ability to underscore the importance of dietary fibre on health but specifically the role of GA as a prebiotic and a promising dietary soluble fibre in the context of the gut-microbiota-brain axis.
Project description:The diets of industrialized countries reflect the increasing use of processed foods, often with the inclusion of novel food additives. Xanthan gum is a complex polysaccharide with unique rheological properties that have established its use as a widespread stabilizer and thickening agent. Xanthan gum’s chemical structure is distinct from the host and dietary polysaccharides that are more commonly expected to transit the gastrointestinal tract, and little is known about its direct interaction with the gut microbiota, which plays a central role in digestion of other dietary fiber polysaccharides. Here, we show that the ability to digest xanthan gum is surprisingly common in industrialized human gut microbiomes and appears contingent on a single uncultured bacterium in the family Ruminococcaceae. Our data reveal that this primary degrader cleaves the xanthan gum backbone before processing the released oligosaccharides using additional enzymes. Surprisingly, some individuals harbor a Bacteroides intestinalis that is incapable of consuming polymeric xanthan gum but grows on oligosaccharide products generated by the Ruminococcaceae. Feeding xanthan gum to germfree mice colonized with a human microbiota containing the uncultured Ruminococcaceae supports the idea that this additive can drive expansion of this primary degrader along with exogenously introduced Bacteroides intestinalis. Our work demonstrates the existence of a potential xanthan gum food chain involving at least two members of different phyla of gut bacteria and provides an initial framework to understand how widespread consumption of a recently introduced food additive influences human microbiomes.
Project description:Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Project description:Guar gum consists mainly of galactomannan, and constitutes the endosperm of guar seeds that acts as a reserve polysaccharide for germination. Due to its molecular structure and physical properties, this biopolymer has been considered as one of the most important and widely used gums in industry. However, for many of these applications this (hemi-)cellulosic structure needs to be modified or (partially) depolymerized in order to customize and improve its physicochemical properties. In this study, transcriptome was employed to decipher the complete enzymatic arsenal for guar gum depolymerization by Aspergillus niger.
Project description:Vertebrates are colonized at birth by complex microbial communities (microbiota) that influence diverse aspects of host biology. We have used a functional genomics approach to identify zebrafish genes that are differentially expressed in response to the microbiota. We assessed RNA expression profiles from zebrafish larvae at 6 days post-fertilization (dpf) that were either raised continuously in the absence of any microorganism (germ-free or GF), or raised GF through 3dpf then colonized with a normal zebrafish microbiota (conventionalized or CONVD). Total RNA was purified from pooled intact zebrafish larvae (28-80 larvae/pool, 3 biological replicate pools/condition) using Trizol reagent (Invitrogen) followed by DNase I digestion (DNA-Free, Ambion) according to manufacturers' protocols. Total RNA from each replicate pool (12ug RNA/replicate) was used as template for independent cDNA synthesis and in vitro transcription reactions (BioArray HighYield RNA Transcript Labeling Kit; Enzo Life Sciences) to generate biotinylated cRNA targets. cRNA targets (20ug/replicate) were fragmented using standard methods. Hybridization and scanning were performed using standard Affymetrix protocol. Raw expression values were normalized (Invariant set method) and modeled (PM-MM model), and present/absent calls were generated using dChip software (build date Dec.11, 2005).
Project description:Vertebrates are colonized at birth by complex microbial communities (microbiota) that influence diverse aspects of host biology. We have used a functional genomics approach to identify zebrafish genes that are differentially expressed in response to the microbiota. We assessed RNA expression profiles from zebrafish larvae at 6 days post-fertilization (dpf) that were either raised continuously in the absence of any microorganism (germ-free or GF), or raised GF through 3dpf then colonized with a normal zebrafish microbiota (conventionalized or CONVD).
Project description:Our work demonstrated an impairment in cognitive, social and emotional behavior in aged sacs knockout zebrafish similar to that observed in human patients. Transcriptomic and proteomic data from the adult brains revealing alterations in several genes related to circadian rhythms and neuroinflammation in adult mutants. t Interestingly, alterations in sleep and circadian rhythms are common in individuals with cerebellar ataxia and may contribute to cognitive function and behavior. Long term treatment with TUDCA , a neuroprotective molecule,partially rescued social and cognitive deficits. These findings suggest the potential for further optimization of this neuroprotective compound in subsequent preclinical and clinical studies.