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Lavelle, A.

Publications and source records attributed to Lavelle, A..

3 recordsLinked to original sources

The South American MicroBiome Archive (saMBA): Enriching the healthy microbiome concept by evaluating uniqueness and biodiversity of neglected populations

The composition and function of the human gut microbiome has been linked to multiple health outcomes across all world regions, often with region-specific associations. Unfortunately, the extent to which microbiomes from different populations are characterised is limited by their economic resources. Over 70% of the sequenced human microbiomes come from analyses of European and North American populations, skewing our understanding by focusing excessively on just 15% of the global population. Thus, entire continents rely on results from research conducted in wealthier countries whose main findings are unlikely to generalize across other world regions. Moreover, statistical models perform poorly when applied to minorities, a blind spot with serious consequences in biomedicine, and which can only be addressed by analysing microbiome data from currently neglected areas. To address this problem, we created saMBA-- the largest archive of gut microbiomes from South America, one of the worlds most biodiverse regions in terms of the gut microbiome of its inhabitants, yet the one with the fewest samples. saMBA includes 33 gut microbiome studies, [~]73% of which were incorporated in a microbiome archive for the first time. By leveraging this resource, we uncovered a high biodiversity within --and uniqueness between-- gut microbiomes across the continent, expanding the concept of the healthy microbiome to be more globally representative. Additionally, our results highlight that the gut microbiome biodiversity of this region remains far from fully characterized. We demonstrate how saMBA can guide new sampling efforts to better capture this diversity. Finally, the code deployed to build saMBA is compatible with that of a previous global compendium and is openly available to researchers from other underrepresented regions, fostering the inclusion of other neglected populations to accelerate microbiome research globally.

bioinformatics↗

Dissecting the respective roles of microbiota and host genetics in the susceptibility of Card9-/- mice to colitis

BackgroundThe etiology of Inflammatory Bowel Disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. ResultsCard9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3{beta} and Reg3{gamma} independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that five weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups own genotype. ConclusionsThese results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or "healthy" microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders.

genetics↗

Faecal microbiota transplantation from Alzheimer's participants induces impairments in neurogenesis and cognitive behaviours in rats

The gut microbiome is emerging as an important susceptibility factor in Alzheimers disease (AD) possibly due to the increased prevalence of pro-inflammatory genera in gut microbiota of AD participants. Microbiota-mediated changes in cognition and adult hippocampal neurogenesis (AHN), an important process for memory which is altered in AD, position the microbiota-gut-brain axis as a key regulator of AD. However, it is unknown whether gut microbiota alterations are the cause or consequence of AD symptoms. We transplanted faecal microbiota from AD participants and age-matched controls into microbiota-depleted naive adult rats and found impairments in AHN and associated memory tasks, which correlated with clinical cognitive scores. Discrete changes in the rat caecal and hippocampal metabolome were evident. Serum from AD participants also decreased neurogenesis in vitro and correlated with cognitive scores and pro-inflammatory genera. Our results reveal that the cognitive symptoms in AD may be due to alterations in gut microbiota, and that impaired neurogenesis may be a mechanistic link between altered gut microbiota and cognitive impairment in AD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/515189v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@143263forg.highwire.dtl.DTLVardef@1842a23org.highwire.dtl.DTLVardef@1ea8aaborg.highwire.dtl.DTLVardef@135e5a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗