| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Heston, M. B., et al.
(author)
-
Gut inflammation associated with age and Alzheimer's disease pathology: a human cohort study
- 2023
-
In: Scientific Reports. - 2045-2322. ; 13:1
-
Journal article (peer-reviewed)abstract
- Age-related disease may be mediated by low levels of chronic inflammation ("inflammaging"). Recent work suggests that gut microbes can contribute to inflammation via degradation of the intestinal barrier. While aging and age-related diseases including Alzheimer's disease (AD) are linked to altered microbiome composition and higher levels of gut microbial components in systemic circulation, the role of intestinal inflammation remains unclear. To investigate whether greater gut inflammation is associated with advanced age and AD pathology, we assessed fecal samples from older adults to measure calprotectin, an established marker of intestinal inflammation which is elevated in diseases of gut barrier integrity. Multiple regression with maximum likelihood estimation and Satorra-Bentler corrections were used to test relationships between fecal calprotectin and clinical diagnosis, participant age, cerebrospinal fluid biomarkers of AD pathology, amyloid burden measured using 11C-Pittsburgh compound B positron emission tomography (PiB PET) imaging, and performance on cognitive tests measuring executive function and verbal learning and recall. Calprotectin levels were elevated in advanced age and were higher in participants diagnosed with amyloid-confirmed AD dementia. Additionally, among individuals with AD dementia, higher calprotectin was associated with greater amyloid burden as measured with PiB PET. Exploratory analyses indicated that calprotectin levels were also associated with cerebrospinal fluid markers of AD, and with lower verbal memory function even among cognitively unimpaired participants. Taken together, these findings suggest that intestinal inflammation is linked with brain pathology even in the earliest disease stages. Moreover, intestinal inflammation may exacerbate the progression toward AD.
|
|
| 5. |
- Kasahara, K., et al.
(author)
-
Gut bacterial metabolism contributes to host global purine homeostasis
- 2023
-
In: Cell Host & Microbe. - 1931-3128. ; 31:6
-
Journal article (peer-reviewed)abstract
- The microbes and microbial pathways that influence host inflammatory disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden is partially driven by gut microbiota and is associated with circulating levels of uric acid (UA) in mice and humans. We identify gut bacterial taxa spanning multiple phyla, including Bacillota, Fusobacteriota, and Pseudomonadota, that use multiple purines, including UA as carbon and energy sources anaerobically. We identify a gene cluster that encodes key steps of anaerobic purine degradation and that is widely distributed among gut-dwelling bacteria. Furthermore, we show that colonization of gnotobiotic mice with purine-degrading bacteria modulates levels of UA and other purines in the gut and systemically. Thus, gut microbes are important drivers of host global purine homeostasis and serum UA levels, and gut bacterial catabolism of purines may represent a mechanism by which gut bacteria influence health.
|
|
| 6. |
- Kasahara, K., et al.
(author)
-
Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model
- 2018
-
In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 3:12, s. 1461-1471
-
Journal article (peer-reviewed)abstract
- Humans with metabolic and inflammatory diseases frequently harbour lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we show that a prominent gut-associated butyrate-producing bacterial genus (Roseburia) is inversely correlated with atherosclerotic lesion development in a genetically diverse mouse population. We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to: impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization; lower systemic inflammation; and ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate reduces endotoxaemia and atherosclerosis development. Together, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis. © 2018, The Author(s), under exclusive licence to Springer Nature Limited.
|
|
| 7. |
- Post, Eric, et al.
(author)
-
The polar regions in a 2°C warmer world
- 2019
-
In: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 5:12
-
Research review (peer-reviewed)abstract
- Over the past decade, the Arctic has warmed by 0.75°C, far outpacing the global average, while Antarctic temperatures have remained comparatively stable. As Earth approaches 2°C warming, the Arctic and Antarctic may reach 4°C and 2°C mean annual warming, and 7°C and 3°C winter warming, respectively. Expected consequences of increased Arctic warming include ongoing loss of land and sea ice, threats to wildlife and traditional human livelihoods, increased methane emissions, and extreme weather at lower latitudes. With low biodiversity, Antarctic ecosystems may be vulnerable to state shifts and species invasions. Land ice loss in both regions will contribute substantially to global sea level rise, with up to 3 m rise possible if certain thresholds are crossed. Mitigation efforts can slow or reduce warming, but without them northern high latitude warming may accelerate in the next two to four decades. International cooperation will be crucial to foreseeing and adapting to expected changes.
|
|
| 8. |
- Vogt, N. M., et al.
(author)
-
Gut microbiome alterations in Alzheimer's disease
- 2017
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age-and sex-matched individuals. We identified phylum-through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
|
|
