7 results on '"Vardhan, Mridula"'
Search Results
2. Intrahepatic microbes govern liver immunity by programming NKT cells
- Author
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Leinwand, Joshua C., Paul, Bidisha, Chen, Ruonan, Xu, Fangxi, Sierra, Maria A., Paluru, Madan M., Nanduri, Sumant, Alcantara, Carolina G., Shadaloey, Sorin A.A., Yang, Fan, Adam, Salma A., Li, Qianhao, Bandel, Michelle, Gakhal, Inderdeep, Appiah, Lara, Guo, Yuqi, Vardhan, Mridula, Flaminio, Zia, Grodman, Emilie R., Mermelstein, Ari, Wang, Wei, Diskin, Brian, Aykut, Berk, Khan, Mohammad, Werba, Gregor, Pushalkar, Smruti, McKinstry, Mia, Kluger, Zachary, Park, Jaimie J., Hsieh, Brandon, Dancel-Manning, Kristen, Liang, Feng-Xia, Park, James S., Saxena, Anjana, Li, Xin, Theise, Neil D., Saxena, Deepak, and Miller, George
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Microbiota (Symbiotic organisms) -- Health aspects -- Physiological aspects ,Host-bacteria relationships -- Research ,Immunity -- Research ,Killer cells -- Health aspects -- Physiological aspects ,Cellular control mechanisms -- Research ,Health care industry - Abstract
The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from that of the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically the bacteroidetes species. Targeting bacteroidetes with oral antibiotics reduced hepatic immune cells by approximately 90%, prevented antigen-presenting cell (APC) maturation, and mitigated adaptive immunity. Mechanistically, our findings are consistent with presentation of bacteroidetes-derived glycosphingolipids to NKT cells promoting CCL5 signaling, which drives hepatic leukocyte expansion and activation, among other possible host-microbe interactions. Collectively, we reveal a microbial/glycosphingolipid/NKT/CCL5 axis that underlies hepatic immunity., Introduction Gut microbiota represent the most abundant and diverse collection of commensal organisms in the body (1). The intestinal microbiome plays a fundamental role in shaping the host immune system [...]
- Published
- 2022
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3. E-cigarettes use in the United States: reasons for use, perceptions, and effects on health
- Author
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Sapru, Sakshi, Vardhan, Mridula, Li, Qianhao, Guo, Yuqi, Li, Xin, and Saxena, Deepak
- Published
- 2020
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4. Electronic cigarette use enriches periodontal pathogens.
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Xu, Fangxi, Pushalkar, Smruti, Lin, Ziyan, Thomas, Scott C., Persaud, Julia Kishanie, Sierra, Maria A, Vardhan, Mridula, Vasconcelos, Rebeca, Akapo, Adenike, Guo, Yuqi, Gordon, Terry, Corby, Patricia M, Kamer, Angela R., Li, Xin, and Saxena, Deepak
- Abstract
The effect of electronic cigarette (e‐cigarette) smoking, especially its long‐term impact on oral health, is poorly understood. Here, we conducted a longitudinal clinical study with two study visits, 6 months apart, to investigate the effect of e‐cigarette use on the bacterial community structure in the saliva of 101 periodontitis patients. Our data demonstrated that e‐cigarette use altered the oral microbiome in periodontitis patients, enriching members of the Filifactor, Treponema, and Fusobacterium taxa. For patients at the same periodontal disease stage, cigarette smokers and e‐cigarette smokers shared more similarities in their oral bacterial composition. E‐cigarette smoking may have a similar potential as cigarette smoking at altering the bacterial composition of saliva over time, leading to an increase in the relative abundance of periodontal disease‐associated pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. The correlation analysis showed that certain genera, such as Dialister, Selenomonas, and Leptotrichia in the e‐cigarette smoking group, were positively correlated with the levels of proinflammatory cytokines, including IFN‐γ, IL‐1β, and TNF‐α. E‐cigarette use was also associated with elevated levels of proinflammatory cytokines such as IFN‐γ and TNF‐α, which contribute to oral microbiome dysbiosis and advanced disease state. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Cross talk between drug‐resistant epilepsy and the gut microbiome.
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Holmes, Manisha, Flaminio, Zia, Vardhan, Mridula, Xu, Fangxi, Li, Xin, Devinsky, Orrin, and Saxena, Deepak
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GUT microbiome ,CROSSTALK ,EPILEPSY ,ANTICONVULSANTS ,BRAIN - Abstract
One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low‐carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted. [ABSTRACT FROM AUTHOR]
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- 2020
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6. The Microbiome, Malignant Fungating Wounds, and Palliative Care.
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Vardhan, Mridula, Flaminio, Zia, Sapru, Sakshi, Tilley, Charles P., Fu, Mei R., Comfort, Christopher, Li, Xin, and Saxena, Deepak
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PALLIATIVE treatment ,BACTERIAL metabolites ,CHRONIC wounds & injuries ,WOUNDS & injuries ,ANAEROBIC bacteria ,WOUND healing ,ODORS ,RIBOSOMAL RNA - Abstract
Malignant fungating wounds present in 5–14% of advanced cancer patients in the United States and are a result of cancerous cells infiltrating and proliferating in the skin. Presentation of malignant fungating wounds often occurs in the last 6 months of life and therefore become symbols of impending death for patients and their families. Due to the incurable and severe nature of these wounds, patients require palliative care until death to minimize pain and suffering. Symptoms associated with these chronic wounds include malodor, pain, bleeding, necrosis, large amounts of exudate, increased microbial growth, and more. Limited research using culture-based techniques has been conducted on malignant fungating wounds and therefore no optimal approach to treating these wounds has been established. Despite limited data, associations between the cutaneous microbiome of these wounds and severity of symptoms have been made. The presence of at least one strain of obligate anaerobic bacteria is linked with severe odor and exudate. A concentration of over 10
5 /g bacteria is linked with increased pain and exudate. Bacterial metabolites such as DMTS and putrescine are linked with components of malignant fungating wound odor and degradation of periwound skin. The few but significant associations made between the malignant fungating wound microbiome and severity of symptoms indicate that further study on this topic using 16S rRNA gene sequencing may reveal potential therapeutic targets within the microbiome to significantly improve current methods of treatment used in the palliative care approach. [ABSTRACT FROM AUTHOR]- Published
- 2019
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7. Electronic Cigarette Use Promotes a Unique Periodontal Microbiome.
- Author
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Thomas SC, Xu F, Pushalkar S, Lin Z, Thakor N, Vardhan M, Flaminio Z, Khodadadi-Jamayran A, Vasconcelos R, Akapo A, Queiroz E, Bederoff M, Janal MN, Guo Y, Aguallo D, Gordon T, Corby PM, Kamer AR, Li X, and Saxena D
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- Adult, Cytokines, Humans, Longitudinal Studies, Periodontitis, Electronic Nicotine Delivery Systems, Microbiota, Periodontium microbiology, Vaping
- Abstract
Electronic cigarettes (e-cigs) have become prevalent as an alternative to conventional cigarette smoking, particularly in youth. E-cig aerosols contain unique chemicals which alter the oral microbiome and promote dysbiosis in ways we are just beginning to investigate. We conducted a 6-month longitudinal study involving 84 subjects who were either e-cig users, conventional smokers, or nonsmokers. Periodontal condition, cytokine levels, and subgingival microbial community composition were assessed, with periodontal, clinical, and cytokine measures reflecting cohort habit and positively correlating with pathogenic taxa (e.g., Treponema, Saccharibacteria , and Porphyromonas ). α-Diversity increased similarly across cohorts longitudinally, yet each cohort maintained a unique microbiome. The e-cig microbiome shared many characteristics with the microbiome of conventional smokers and some with nonsmokers, yet it maintained a unique subgingival microbial community enriched in Fusobacterium and Bacteroidales (G-2). Our data suggest that e-cig use promotes a unique periodontal microbiome, existing as a stable heterogeneous state between those of conventional smokers and nonsmokers and presenting unique oral health challenges. IMPORTANCE Electronic cigarette (e-cig) use is gaining in popularity and is often perceived as a healthier alternative to conventional smoking. Yet there is little evidence of the effects of long-term use of e-cigs on oral health. Conventional cigarette smoking is a prominent risk factor for the development of periodontitis, an oral disease affecting nearly half of adults over 30 years of age in the United States. Periodontitis is initiated through a disturbance in the microbial biofilm communities inhabiting the unique space between teeth and gingival tissues. This disturbance instigates host inflammatory and immune responses and, if left untreated, leads to tooth and bone loss and systemic diseases. We found that the e-cig user's periodontal microbiome is unique, eliciting unique host responses. Yet some similarities to the microbiomes of both conventional smokers and nonsmokers exist, with strikingly more in common with that of cigarette smokers, suggesting that there is a unique periodontal risk associated with e-cig use.
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- 2022
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