Browsing by Subject "Bacteroidetes"

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    Dihydroceramides Derived from Bacteroidetes Species Sensitize TRPV1 Channels
    (MDPI, 2023-01-03) Ludwig, Nora; Demaree, Isaac S.; Yamada, Chiaki; Nusbaum, Amilia; Nichols, Frank C.; White, Fletcher A.; Movila, Alexandru; Obukhov, Alexander G.; Anatomy, Cell Biology and Physiology, School of Medicine
    Bacterial colonization of open wounds is common, and patients with infected wounds often report significantly elevated pain sensitivity at the wound site. Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels are known to play an important role in pain signaling and may be sensitized under pro-inflammatory conditions. Bacterial membrane components, such as phosphoethanolamine dihydroceramide (PEDHC), phosphoglycerol dihydroceramide (PGDHC), and lipopolysaccharide (LPS), are released in the environment from the Gram-negative bacteria of the Bacteroidetes species colonizing the infected wounds. Here, we used intracellular calcium imaging and patch-clamp electrophysiology approaches to determine whether bacterially derived PEDHC, PGDHC, or LPS can modulate the activity of the TRPV1 channels heterologously expressed in HEK cells. We found that PEDHC and PGDHC can sensitize TRPV1 in a concentration-dependent manner, whereas LPS treatment does not significantly affect TRPV1 activity in HEK cells. We propose that sensitization of TRPV1 channels by Bacteroidetes-derived dihydroceramides may at least in part underlie the increased pain sensitivity associated with wound infections.
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    Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice
    (American Diabetes Association, 2018-09) Beli, Eleni; Yan, Yuanqing; Moldovan, Leni; Vieira, Cristiano P.; Gao, Ruli; Duan, Yaqian; Prasad, Ram; Bhatwadekar, Ashay; White, Fletcher A.; Townsend, Steven D.; Chan, Luisa; Ryan, Caitlin N.; Morton, Daniel; Moldovan, Emil G.; Chu, Fang-I; Oudit, Gavin Y.; Derendorf, Hartmut; Adorini, Luciano; Wang, Xiaoxin X.; Evans-Molina, Carmella; Mirmira, Raghavendra G.; Boulton, Michael E.; Yoder, Mervin C.; Li, Qiuhong; Levi, Moshe; Busik, Julia V.; Grant, Maria B.; Pediatrics, School of Medicine
    Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR end points, including acellular capillaries and leukocyte infiltration. We hypothesized that IF-mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia. Compared with db/db mice on ad libitum feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number, villi length, and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid (BA) metabolism, measurement of BAs demonstrated a significant increase of tauroursodeoxycholate (TUDCA), a neuroprotective BA, in db/db on IF but not in db/db on AL feeding. TGR5, the TUDCA receptor, was found in the retinal primary ganglion cells. Expression of TGR5 did not change with IF or diabetes. However, IF reduced retinal TNF-α mRNA, which is a downstream target of TGR5 activation. Pharmacological activation of TGR5 using INT-767 prevented DR in a second diabetic mouse model. These findings support the concept that IF prevents DR by restructuring the microbiota toward species producing TUDCA and subsequent retinal protection by TGR5 activation.