The gut microbiota modulates environmental risk for cognitive impairment
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE163099 | GEO | 2021/04/01
REPOSITORIES: GEO
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Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
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2020-04-17 | GSE147183 | GEO
Project description:Significant gut microbiota heterogeneity exists amongst UC patients though the clinical implications of this variance are unknown. European and South Asian UC patients exhibit distinct disease risk alleles, many of which regulate immune function and relate to variation in gut microbiota β-diversity. We hypothesized ethnically distinct UC patients exhibit discrete gut microbiotas with unique luminal metabolic programming that influence adaptive immune responses and relate to clinical status. Using parallel bacterial 16S rRNA and fungal ITS2 sequencing of fecal samples (UC n=30; healthy n=13), we corroborated previous observations of UC-associated depletion of bacterial diversity and demonstrated significant gastrointestinal expansion of Saccharomycetales as a novel UC characteristic. We identified four distinct microbial community states (MCS 1-4), confirmed their existence using microbiota data from an independent UC cohort, and show they co-associate with patient ethnicity and degree of disease severity. Each MCS was predicted to be uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of metabolic products from these pathways. Using a novel in vitro human DC/T-cell assay we show that DC exposure to patient fecal water led to MCS -specific changes in T-cell populations, particularly the Th1:Th2 ratio, and that patients with the most severe disease exhibited the greatest Th2 skewing. Thus, based on ethnicity, microbiome composition, and associated metabolic dysfunction, UC patients may be stratified in a clinically and immunologically meaningful manner, providing a platform for the development of FMC-focused therapy. Fecal microbiome was assessed with Affymetrix PhyloChip arrays from patients with ulcerative colitis and healthy controls.
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Project description:Colorectal cancer (CRC) is one of the most common cancer worldwide. Initiation and progression of CRC involve complex interactions among genetic, epigenetic and environmental factors. Given that hereditary and familial CRC only accounts for 2% to 5% of cases, environmental factors are the key triggers of CRC. Emerging evidence has indicated that gut microbes are an important environmental factor promoting CRC development. Gut dysbiosis has been shown to promote colorectal carcinogenesis in mice. Several individual bacterial species, such as the enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum and Peptostreptococcus anaerobius, could exert carcinogenic effects by inducing direct DNA damage, oxidative damage and activating oncogenic signaling pathways. Recent studies have shown that the appendix plays an important role in maintaining homeostasis and biodiversity of gut microbiome by providing an ideal ecological niche for commensal bacteria and production of immunoglobulin A. Considering the key role of microorganisms in gastrointestinal pathophysiology, absence of appendix may result in disruption of microbiome homeostasis, which could potentially influence the risk of developing CRC. In terms of epidemiological evidence, the association of appendectomy with the risk of CRC development has been controversial, and to date no consensus has been attained. Although gut microorganisms could be a crucial pivot between appendectomy and risk of subsequent CRC development, the direct contribution of appendectomy and the underlying mechanisms are still largely unexplored. In this study, we aim to study
1. the association between appendectomy and colorectal cancer, and
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2024-02-08 | GSE245831 | GEO
Project description:The mammalian gastrointestinal tract contains a diverse ecosystem of microbial species collectively making up the gut microbiome. Emerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Consumption of unhealthy yet palatable dietary factors associated with obesity and metabolic dysfunction (e.g., saturated fat, added sugar) produces microbiota dysbiosis and negatively impacts neurocognitive function, particularly when consumed during early life developmental periods. Here we explore whether excessive early life consumption of added sugars negatively impacts neurocognitive development via the gut microbiome. Using a rodent model of habitual sugar-sweetened beverage (SSB) consumption during the adolescent stage of development, we first show that excessive early life sugar intake impairs hippocampal-dependent memory function when tested during adulthood while preserving other neurocognitive domains. Gut microbiome genomic sequencing analyses reveal that early life SSB consumption alters the abundance of various bacterial populations, including elevations in operational taxonomic units within the genus Parabacteroides (P. distasonis and P. johnsonii) whose abundance negatively correlated with memory task performance. Additional results reveal that in vivo Parabacteroides enrichment of cultured P. distasonis and P. johnsonii bacterial species in adolescent rats severely impairs memory function during adulthood. Hippocampus transcriptome analyses identify gene expression alterations in neurotransmitter synaptic signaling, intracellular kinase signaling, metabolic function, neurodegenerative disease, and dopaminergic synaptic signaling-associated pathways as potential mechanisms linking microbiome outcomes with memory impairment. Collectively these results identify microbiota dysbiosis as a mechanism through which early life unhealthy dietary patterns negatively impact neurocognitive outcomes.
2021-02-25 | GSE150091 | GEO