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Clarke, G.

Publications and source records attributed to Clarke, G..

5 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↗

The Neuroactive Potential of the Elderly Human Gut Microbiome is Associated with Mental Health Status

Ageing is usually associated with physiological decline, increased mental health issues, and cognitive deterioration, alongside specific changes in the gut microbiome. However, the relationship between the neuroactive potential of the gut microbiome and mental health and cognition among the elderly remains less explored. This study examines a cohort of 153 older Chilean adults with cognitive complaints, assessing anthropometric data, mental health via five distinct tests, and gut microbiome composition through 16SV4 sequencing. Our findings reveal associations between anthropometric factors and depression scores in mental tests of participants with their gut microbiome composition. Notably, depression was associated with changes in the abundance of Lachnospiraceae Eubacterium xylanophilum group and Fusobacteriaceae Fusobacterium. Additionally, bacterial pathways involved in metabolising neuroactive compounds such as tryptophan, short-chain fatty acids, p-cresol, glutamate, and nitric oxide were associated with participant age, sex, and cognitive performance. Moreover, participants sex was associated with the neuroactive potential of specific bacteria, suggesting a role of the gut microbiome in sex-related mental health differences in the elderly. Together, to the best of our knowledge, this study demonstrates for the first time the association between the neuroactive potential of the human gut microbiome and mental health status in older individuals with cognitive complaints.

animal behavior and cognition↗

Distinct Dendritic Morphological Changes in the Nucleus Accumbens of Microbiota-deficient Male Mice

The gut microbiota has been shown to be an important regulator of brain and behaviour. Germ-free rodents are a key model to study the microbiome-gut-brain axis to reveal the microbial underpinnings of diseases, including those related to psychiatric illnesses. The present study evaluated whether the absence of gut microbiota could alter the morphological development of the nucleus accumbens, a brain region located in the ventral striatum involved in stress, mood and addiction. In germ-free mice, there was dendritic hypertrophy of medium spiny neurons in the shell and dendritic elongation in the core. This led to an increase in the number of stubby dendritic spines within the shell and an increase in both stubby and thin spines in the core. Taken together, these results indicate that the gut microbiota is essential for the normal development of the dendritic structure of medium spiny neurons in the nucleus accumbens and that altered remodelling may contribute to maladaptive psychiatric disorders.

neuroscience↗

Kronos: A computational tool to facilitate biological rhythmicity analysis

MotivationCircadian rhythms, or 24-hour biological cycles, are key in maintaining health in almost all living organisms and synchronize important physiological and behavioural processes daily. Interest in circadian rhythm research is expanding as our urban environments have increased exposure to factors that can disrupt the normal physiological rhythm of our body, such as delayed bedtimes, shift work, jet-lag, increased screen-time, and exposure to artificial light. Discovering how oscillatory signals respond to both external and internal factors can lead to important biological breakthroughs, but assessing rhythmicity can be both limited by the complexity of statistical models and demanding in terms of coding and statistical expertise. ImplementationHere, we describe the development of a novel easy-to-use R-based tool, Kronos, to assess circadian rhythms in biological data sets. Kronos provides the user with new functionalities not currently available, including the analysis of two or more groups in complex study designs, handling both independent and repeated-measures data, as well as ranging from single variables to high dimensional omics data sets. Kronos is a novel tool to facilitate the analysis of rhythmicity in simple and complex experimental designs and enables researchers from diverse scientific fields to interrogate rhythmicity. Availabilityhttps://github.com/thomazbastiaanssen/kronos

bioinformatics↗

Integrated Multi-Omics Analysis of Brain Aging in Female Nonhuman Primates Reveals Altered Signaling Pathways Relevant to Age-Related Disorders

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis (WGCNA) to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found GABA tissue content associated with these signaling pathways, providing one potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

systems biology↗