Microbiota and the Urogenital Tract, Pathogenesis, and Therapies

Tungland, Bryan

doi:10.1016/b978-0-12-814649-1.00014-4

Cited by 8 publications

(11 citation statements)

References 416 publications

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“…While the presence of these species is not a direct harbinger, loss or overabundance of these species have been reported to play a key role in the persistence of inflammatory responses seen in chronic diseases of the brain and gut [ 34 ]. For example, our data show age-induced increases in Dorea (Multiple sclerosis), Butyricicoccus pullicaecorum (inflammatory bowel disease), Allobaculum (Alzheimer’s disease), Candidatus Arthromitus (systemic inflammation), Streptococcus , Clostridium (traumatic brain injury), Bacteroides (Alzheimer’s disease), Parabacteriodes gordonii (Inflammatory Bowel Disease)), Prevotella (systemic inflammation), and Bacteroides ovatus (metabolic disease and Alzheimer’s disease) [ 22 , 35 - 37 ]. On the other hand, the bacteria Lactobacillus , which is often used as a probiotic, and Parabacteroides distasonis have been linked to positive effects on anxiety and depression and have been shown to possibly alleviate obesity and metabolic disease in mice [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, decreases in other bacterial species correlated with inflammatory diseases were seen in the young TBI group compared to young shams. These included decreases in Coprobaccillus (inflammatory bowel disease and systemic inflammation), Blautia (Obesity), and Dehalobacterium (systemic inflammation) [ 37 , 40 ]. These variances were unique to the young mice post-injury and occurred in conjunction with unfavorable histologic outcomes in the young TBI mice [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Future studies verifying the possible benefits of probiotic treatment post-injury may necessitate stratification of probiotic strains by age. The generous addition of even beneficial bacteria could lead to further dysbiosis and pathology [ 25 , 37 , 40 - 42 ]. The limitations of the present study merit consideration.…”

Section: Discussionmentioning

confidence: 99%

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Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice

Davis

Islam

Das

et al. 2021

Journal of Experimental Neurology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice

Davis

Islam

Das

et al. 2021

Journal of Experimental Neurology

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“…Additionally, biochemical modification of statins by gut bacteria could potentially contribute to side effects of the drug 18 . Independent of statins, the gut microbiome has a well characterized role in contributing to host metabolic health through regulating insulin sensitivity, blood glucose, and inflammation, hence sharing considerable overlap with off-target effects of statin therapy 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity in statin responses explained by variation in the human gut microbiome

Wilmanski

Kornilov

Diener

et al. 2021

Preprint

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Statins remain one of the most prescribed medications worldwide. While effective in decreasing atherosclerotic cardiovascular disease risk, statin use is associated with several side effects for a subset of patients, including disrupted metabolic control and increased risk of type II diabetes. We investigated the potential role of the gut microbiome in modifying patient response to statin therapy. In a cohort of >1840 individuals, we find that the hydrolyzed substrate for 3-hydroxy-3-methylglutarate-CoA (HMG-CoA) reductase, HMG, may serve as a reliable marker for statin on-target effects. Through exploring gut microbiome associations between blood-derived measures of statin effectiveness and metabolic health parameters among statin users and non-users, we find that heterogeneity in statin response is associated with variation in the gut microbiome. A Bacteroides rich, α-diversity depleted, microbiome composition corresponds to the strongest statin on-target response, but also greatest disruption to glucose homeostasis, indicating lower treatment doses and/or complementary therapies may be beneficial in those individuals. Our findings suggest a potential path towards personalizing statin treatment through gut microbiome monitoring.Between 25% - 30% of older adults across the United States and Europe take statins regularly for the purpose of treating or preventing atherosclerotic cardiovascular disease (ACVD), making statins one of the most prescribed medications in the developed world 1,2. While statins have proven to be highly effective in decreasing ACVD-associated mortality, considerable heterogeneity exists in terms of efficacy (i.e., lowering low density lipoprotein (LDL) cholesterol) 3. Furthermore, statin use can give rise to a number of side effects in a subset of patients, including myopathy, disrupted glucose control, and increased risk of developing type II diabetes (T2D) 4–8. Several guidelines exist for which at-risk populations should be prescribed statins and at what intensity 9. However, despite considerable progress in identifying pharmacological 10 and genetic factors 11 contributing to heterogeneity in statin response, personalized approaches to statin therapy remain limited. Many times, treatment decisions are made through trial and error between the clinician and patient to obtain an optimal tolerable dose 12. Avoiding this trial-and-error phase through individualized analysis of genetic, physiological, and health parameters has the potential to improve drug tolerance, adherence, and long-term health benefits, as well as guide complementary therapies aimed at mitigating side effects.Several studies have recently demonstrated a link between the gut microbiome and statin use 13,14. Similar to other prescription drugs, statins are widely metabolized by gut bacteria into secondary compounds 15,16. This indicates that the gut microbiome may impact statin bioavailability or potency to its host, contributing to the interindividual variability in LDL response seen among statin users 17. Additionally, biochemical modification of statins by gut bacteria could potentially contribute to side effects of the drug 18. Independent of statins, the gut microbiome has a well characterized role in contributing to host metabolic health through regulating insulin sensitivity, blood glucose, and inflammation, hence sharing considerable overlap with off-target effects of statin therapy 19,20.Statin intake has also been implicated in shifting gut microbiome composition, where primarily obese individuals taking statins were less likely to be classified into a putative gut microbiome compositional state, or ‘enterotype’, defined by high relative abundance of Bacteroides and a depletion of short-chain fatty acid (SCFA) producing Firmicutes taxa 21. However, contradictory findings in animal models have also been reported, where a statin intervention decreased abundance of SCFA-producing taxa and, consequently, the gut ecosystem’s capacity to produce butyrate 22.Given the numerous documented interactions between the gut microbiome and statins, and the established effect of the gut microbiome on metabolic health, we sought to explore the potential role of the gut microbiome in modifying the effect of statins on inhibiting their target enzyme 3-hydroxy-3-methylglutarate-CoA (HMG-CoA) reductase, as well as influencing the negative side effects of statins on metabolic health parameters. We analyzed data from over 1840 deeply-phenotyped individuals with extensive medication histories, clinical laboratory tests, plasma metabolomics, whole genome and stool 16S rRNA gene amplicon sequencing data. We found that heterogeneity in statin on-target effects and off-target metabolic disruption could be explained by variation in the composition of the gut microbiome. Overall, our results suggest that, with further study and refinement, the taxonomic composition of the gut microbiome may be used to inform personalized statin therapies.

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“…In addition, the source of lactobacilli populations residing in these regions is not clear. Nonetheless, commensal microbes, including some Lactobacillus spp ., can modulate host immune responses and directly or indirectly inhibit colonization and invasion by pathogens [ 7 ]. Indirect inhibition occurs when host attachment sites are occupied by commensals that compete for nutrients and growth factors, produce unique metabolites to enhance survival, and stimulate the production of factors with pro-inflammatory and antimicrobial effects [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus strains vary in their ability to interact with human endometrial stromal cells

Shiroda

Manning

2020

PLoS ONE

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The placental membranes that surround the fetus during pregnancy were suggested to contain a low abundance microbiota. Specifically, abundance of Lactobacillus , a probiotic and dominant member of the microbiome of the lower reproductive tract, has been shown to correlate with healthy, term pregnancies. We therefore sought to assess the interactions between four different Lactobacillus strains with immortalized decidualized endometrial cells (dT-HESCs), which were used as a model to represent the outermost layer of the placental membranes. Notably, we demonstrated that all four Lactobacillus strains could associate with dT-HESCs in vitro . L . crispatus was significantly more successful (p < 0.00005), with 10.6% of bacteria attaching to the host cells compared to an average of 0.8% for the remaining three strains. The four strains also varied in their ability to form biofilms. Dependent on media type, L . reuteri 6475 formed the strongest biofilms in vitro . To examine the impact on immune responses, levels of total and phosphorylated protein p38, a member of the Mitogen Activated Protein Kinase (MAPK) pathway, were examined following Lactobacillus association with dT-HESCs. Total levels of p38 were reduced to an average of 44% that of the cells without Lactobacillus (p < 0.05). While a trend towards a reduction in phosphorylated p38 was observed, this difference was not significant (p > 0.05). In addition, association with Lactobacillus did not result in increased host cell death. Collectively, these data suggest that varying types of Lactobacillus can attach to the outermost cells of the placental membranes and that these interactions do not contribute to inflammatory responses or host cell death. To our knowledge this is the first in vitro study to support the ability of Lactobacillus to interact with placental cells, which is important when considering its use as a potential probiotic within the reproductive tract.

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Microbiota and the Urogenital Tract, Pathogenesis, and Therapies

Cited by 8 publications

References 416 publications

Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice

Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice

Heterogeneity in statin responses explained by variation in the human gut microbiome

Lactobacillus strains vary in their ability to interact with human endometrial stromal cells

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