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The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It differentiates between these foreign substances through a complex system of pattern recognition receptors expressed on the surface of the intestinal epithelial cells as well as the underlying immune cells. These immune cells actively sample and evaluate microbes and other particles that pass through the lumen of the gut. This local sensing system is part of a broader distributed signaling system that is connected to the rest of the body through the enteric nervous system, the immune system, and the metabolic system. While local tissue homeostasis is maintained by commensal bacteria that colonize the gut, colonization itself may not be required for the activation of distributed signaling networks that can result in modulation of peripheral inflammation. Herein, we describe the ability of a gut-restricted strain of commensal bacteria to drive systemic anti-inflammatory effects in a manner that does not rely upon its ability to colonize the gastrointestinal tract or alter the mucosal microbiome. Orally administered EDP1867, a gamma-irradiated strain of Veillonella parvula, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora. In murine models of inflammatory disease including delayed-type hypersensitivity (DTH), atopic dermatitis, psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted in significant reduction in inflammation and immunopathology. Ex vivo cytokine analyses revealed that EDP1867 treatment diminished production of pro-inflammatory cytokines involved in inflammatory cascades. Furthermore, blockade of lymphocyte migration to the gut-associated lymphoid tissues impaired the ability of EDP1867 to resolve peripheral inflammation, supporting the hypothesis that circulating immune cells are responsible for promulgating the signals from the gut to peripheral tissues. Finally, we show that adoptively transferred T cells from EDP1867-treated mice inhibit inflammation induced in recipient mice. These results demonstrate that an orally-delivered, non-viable strain of commensal bacteria can mediate potent anti-inflammatory effects in peripheral tissues through transient occupancy of the gastrointestinal tract, and support the development of non-living bacterial strains for therapeutic applications.

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Background: Wernicke’s encephalopathy (WE) is an acute neuropsychiatric derangement caused by Vitamin-B1 (Thiamine) deficiency. Clinical Case: A 49-year-old Hispanic woman was admitted with abdominal pain, intractable nausea and vomiting, two weeks following a diagnosis of infectious mononucleosis. An upper endoscopy was negative. She was discharged on symptomatic treatment with pantoprazole and sucralfate. Four weeks later, she presented with worsening symptoms and a new complaint of blurry vision. Physical exam revealed decreased visual acuity with dysconjugate gaze. Brain CT and MRI were unremarkable. Outpatient ophthalmology consultation was advised. Four days later, she reported to the ophthalmologist with worsening vision, headaches, distal tingling/numbness, gait instability, mildly impaired cognition. The ocular examination revealed visual acuity restricted to counting fingers, large central scotoma, restricted abduction/adduction, and bilateral horizontal and vertical nystagmus. She was readmitted with a suspicion of Miller-Fischer variant of Guillain-Barre. She denied alcohol consumption, tobacco or recreational drug use. She reported 40lb weight loss in 5 weeks. On physical exam, strength was normal, with decreased distal vibration sensation, absent ankle reflexes and ataxic gait. Anti-GQ1b antibodies and CSF studies were unremarkable. Further testing revealed negative/normal HIV antigen/antibody, vitamin B12 level, glycohemoglobin A1c, Lyme antibodies, angiotensin converting enzyme, ANA and serum protein electrophoresis. Serial brain MRI showed FLAIR hyperintensity in both thalami, dorsal medial brainstem along the mammillary bodies, and the third periventricular white matter. Thiamine deficiency was strongly suspected. A vitamin-B1 level was sent out and she was empirically started on large dose IV thiamine. The thiamine level returned very low at 24nmol/l (70-180nmol/l) confirming WE. Her symptoms began to resolve within 12 hours of thiamine infusion. Given no preceding history of alcoholism, a workup for other causes of thiamine deficiency was pursued. Celiac serology, stool pancreatic elastase, CT chest/abdomen/pelvis, colonoscopy were unremarkable. Thiamine deficiency was attributed to her prolonged history of vomiting, decreased intake, in combination with the recently prescribed pantoprazole and sucralfate which contributed to malabsorption. Discussion: WE is typically related to alcoholism. From 1867-2014, 623 cases of WE were described in non-alcoholics. We should have a high index of suspicion for thiamine deficiency in situations of unbalanced nutrition that has lasted for 2 to 3 weeks to avoid misdiagnosis of the life-threatening WE or irreversible brain damage (Korsakoff syndrome). This should prompt immediate administration of large doses of thiamine parenterally even prior to laboratory confirmation.

Background: Quorum sensing is a cell-to-cell communication, which is extensively observed in bacteria. This process allows the cell to detect, analyze, share and act upon various environmental stimuli based on cell density. The molecular aspect of this process is the secretion and detection of chemical signaling molecules called autoinducers (AIs), which act upon the gene expression. The quorum sensing signaling pathway is specifically observed only bulk population or in other words, the quorum sensing is effective only in high cell density. The quorum sensing circuit in the bacterial population is widely studied under the following heading; quorum sensing in Gram positive bacterium, Quorum sensing in Gram negative bacterium and the Quorum sensing with respect to Interkingdom communication. These models are studied using the widely studied models like Vibrio fischeri in Gram negative QS circuit, Staphylococcus aureus in Gram positive QS circuit and Vibrio harveyi. This review paper details the introduction of quorum sensing and their gene level explanation and how they effect on the virulence of a particular species of bacteria. This paper also throws light on the realization that the bacteria has the capable of performing coordinated activities that was so long contributed to the eukaryotic cell performance.