Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders.

IL-22 is critical for ameliorating obesity-induced metabolic disorders. However, it is unknown where IL-22 acts to mediate these outcomes. Here we examine the importance of tissue-specific IL-22RA1 signaling in mediating long-term high fat diet (HFD) driven metabolic disorders. To do so, we generated intestinal epithelium-, liver-, and white adipose tissue (WAT)-specific Il22ra1 knockout and littermate control mice. Intestinal epithelium- and liver-specific IL-22RA1 signaling upregulated systemic glucose metabolism. Intestinal IL-22RA1 signaling also mediated liver and WAT metabolism in a microbiota-dependent manner. We identified an association between Oscillibacter and elevated WAT inflammation, likely induced by Mmp12 expressing macrophages. Mechanistically, transcription of intestinal lipid metabolism genes is regulated by IL-22 and potentially IL-22-induced IL-18. Lastly, we show that Paneth cell-specific IL-22RA1 signaling, in part, mediates systemic glucose metabolism after HFD. Overall, these results elucidate a key role of intestinal epithelium-specific IL-22RA1 signaling in regulating intestinal metabolism and alleviating systemic obesity-associated disorders.

Bacteriophages as therapeutic & disinfectant agents to tackle multidrug-resistant Acinetobacter baumannii.

Background & objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is a serious threat for human health worldwide. The studies on agents targeting A. baumannii are imperative due to identified A. baumannii co-infections in COVID-19. Bacteriophages are promising antibacterial agents against drug-resistant bacteria. This study intended to isolate bacteriophages against MDR A. baumannii from the water of river Ganga, to be used potentially as therapeutic and disinfectant particles. Methods: Acinetobacter phages were isolated from the Ganga water collected from Kanpur and further tested on 50 MDR A. baumannii isolates to determine host range. The phages were morphologically characterized by transmission electron microscopy. The disinfectant property of the isolated phages was tested by spraying of bacteriophage cocktail on MDR A. baumannii contaminated plastic surface, analyzed by colony-forming unit (CFU) and bioluminescence assay (adenosine triphosphate monitoring). Results: A total of seven bacteriophages were isolated against MDR A. baumannii. The bacteriophages lysed three MDR A. baumannii isolates out of 50 tested, showing narrow host range. Electron microscopy revealed hexagonal heads and long tails of bacteriophages, belonging to order Caudovirales. The bacteriophage cocktail reduced the MDR A. baumannii load efficiently on plastic surface, evidenced by reduction in CFUs and bioluminescence. Interpretation & conclusions: The findings of this study suggest that the isolated bacteriophages are potential lytic agents for MDR A. baumannii clinical isolates, and may be used as potential therapeutic agents as well as disinfectant to combat MDR A. baumannii with due consideration to phage host specificity, with further characterization.

Molecular characterization of Clostridioides difficile by multi-locus sequence typing (MLST): A study from tertiary care center in India.

OBJECTIVES: Clostridioides difficile is an important pathogen responsible for antibiotic-associated diarrhoea (AAD). This study was aimed to perform multi-locus sequence typing (MLST) of C. difficile isolates from AAD cases and to understand the clonal relationship between these C. difficile strains. METHODS: Thirty five strains and a standard strain C.difficile ATCC 9689 were characterized by polymerase chain reaction assay (PCR) for toxin genes (tcdA and tcdB gene) detection and MLST. RESULTS: MLST results revealed that the most common sequence types were ST-17, ST-54, ST-63. The cluster analysis revealed that strains isolated from AAD patients generated 12 MLST sequence types grouped into two distinct evolutionary lineages. CONCLUSIONS: ST 17 is most prominent sequence type. This is the first report of MLST based study of C. difficile from India. Further studies from diverse geographical regions can help better understand the epidemiology of CDI in India.

IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment.

The Th17 cell-lineage-defining cytokine IL-17A contributes to host defense and inflammatory disease by coordinating multicellular immune responses. The IL-17 receptor (IL-17RA) is expressed by diverse intestinal cell types, and therapies targeting IL-17A induce adverse intestinal events, suggesting additional tissue-specific functions. Here, we used multiple conditional deletion models to identify a role for IL-17A in secretory epithelial cell differentiation in the gut. Paneth, tuft, goblet, and enteroendocrine cell numbers were dependent on IL-17A-mediated induction of the transcription factor ATOH1 in Lgr5+ intestinal epithelial stem cells. Although dispensable at steady state, IL-17RA signaling in ATOH1+ cells was required to regenerate secretory cells following injury. Finally, IL-17A stimulation of human-derived intestinal organoids that were locked into a cystic immature state induced ATOH1 expression and rescued secretory cell differentiation. Our data suggest that the cross talk between immune cells and stem cells regulates secretory cell lineage commitment and the integrity of the mucosa.

Infective Endocarditis Caused by C. sordellii: The First Case Report from India.

Clostridium sordellii is a gram-positive anaerobic bacteria most commonly isolated from skin and soft tissue infection, penetrating injurious and intravenous drug abusers. The exotoxins produced by the bacteria are associated with toxic shock syndrome. We report here a first case of infective endocarditis due to C. sordellii from a female patient with ventricular septal defect from India.

Immunoglobulin Receptors Expression in Indian Colon Cancer Patients and Healthy Subjects Using a Noninvasive Approach and Flowcytometry.

BACKGROUND: Isolation of viable colonocytes from human stool is a noninvasive and convenient approach that can be used for diagnostic, screening, management, and research on various gastrointestinal (GI) diseases including colon cancer. Limited studies are available globally and for the first time in this article, we have reported the immunoglobulin (Ig) (IgA and IgG) receptors concentration on viable colonocytes for Indian colon cancer patients using this noninvasive approach. MATERIALS AND METHODS: Viable colonocytes from stool were isolated by the Somatic Cell Sampling and Recovery method (Noninvasive Technology, USA) and processed for the assessment of Igs (IgA and IgG) receptors expression using standard immunophenotyping and flow cytometry. RESULTS: IgA and IgG receptor expression was measured and reported on these viable colonocytes. There was a significant difference in the expression of IgA and IgG receptors on viable colonocytes between colon cancer patients and healthy individuals. CONCLUSION: This noninvasive technique is a promising approach for the detection of molecular and immunological markers that will help clinicians in the diagnosis, screening, monitoring, and management of different GI diseases including colon cancer.

Mortality due to scrub typhus - report of five cases.

Scrub typhus is largely ignored in India particularly during outbreaks of viral fever. The disease course is often complicated leading to fatalities in the absence of treatment. However, if diagnosed early and a specific treatment is initiated, the cure rate is high. We report here five cases of scrub typhus to highlight the fact that high clinical suspicion for such a deadly disease is an absolute necessity.

Toll like receptors (TLRs) in response to human gut microbiota of Indian obese and lean individuals.

BACKGROUND: The rising incidence of obesity is one of the most serious public health issues in the developed as well as in developing countries like India. Obesity and overweight are most important risk factors for many chronic diseases, including cardiovascular diseases, diabetes and cancer. In this study the body mass index (BMI) cut off was taken as 18.5-22.9 kg/m2 for normal, 23.0-24.9 kg/m2 for Overweight and >25 kg/m2 for obese as per WHO recommendation for Asian Indians, which is different for developed and developing countries. Role of gut microbiota mediated immune response in the development of obesity has been studied but the literature on Indian population are lacking. Therefore, a study was conducted to determine Toll like receptors (TLRs) in response to human gut microbiota of Indian obese and lean individuals using viable colonocytes in a Non invasive technique and Flowcytometry. METHODS: A total of 20 healthy volunteer (10 obese and 10 lean) were enrolled in the study as per inclusion and exclusion criteria. Viable colonocytes were isolated from fecal samples using a Non invasive technique (SCSR Method). Toll like receptors (TLRs) and immunoglobulin (IgA &IgG) receptor concentration were measured by standard Flowcytometry methods using specific fluorochrome conjugated antibodies. RESULTS: Average TLR2 receptor concentration was significantly higher in obese (6.35 %) as compared to lean (2.9 %) (P = 0.01). TLR4 receptor concentration was 1.4 % in obese and 1.65 % in lean although the difference was not statistically significant (P = 0.59). IgA & IgG receptor concentration was 49.6 % & 11.2 % in the obese and 67.15 % & 8.05 % in the lean respectively but the differences among both the group were not statistically significant. CONCLUSION: The results of the present study will be helpful for physicians and researchers to find some biomarkers which can determine predisposition of the obesity in Indian population and helps to use alternative therapeutics such as probiotics to maintain gut homeostasis and immune modulation to prevent obesity.

Concurrent syphilis and Chlamydia trachomatis infection in bisexual male: A rare case of proctitis.

Unsafe sexual practices in men who have sex with men population lead to emergence of high-risk networks for sexually transmitted infection transmission. The atypical clinical presentation of proctitis, the unawareness of physicians and patients in this regard, and the nonavailability of molecular diagnostic methods in routine practice may have contributed to its underdiagnosis. We report a case of syphilis in a bisexual male with a concurrent rectal Chlamydia trachomatis infection not previously reported from India. Reporting such cases has public health importance.

Linezolid-resistant Enterococcus faecalis in leukemia patients: Rare cases with review of literature.

Resistance to linezolid is rare in clinical isolates of Enterococcus faecalis. Here, we report cases of linezolid resistant Enterococcus fecalis in leukemia patients with review of literature.

Bartonella henselae infection in diverse clinical conditions in a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: : Bartonella henselae causes infections which closely resemble febrile illness and chronic diseases such as tuberculosis and haematological malignancies. There are not many studies on Bartonella infections from India. The present study was undertaken to diagnose B. henselae infection in diverse clinical conditions in a tertiary care hospital in north India. METHODS: A total of 145 patients including those with fever and lymphadenopathy, infective endocarditis and neuroretinitis were enrolled in the study. Whole blood, serum and lymph node aspirate and valvular vegetations if available, were obtained. Samples were plated on chocolate agar and brain-heart infusion agar containing five per cent fresh rabbit blood and were incubated at 35°C for at least four weeks in five per cent CO2with high humidity. Immunofluorescent antibody assay (IFA) was done for the detection of IgM antibodies in the serum using a commercial kit. Whole blood was used to perform polymerase chain reaction (PCR) for the citrate synthase gene (gltA). RESULTS: IFA was positive in 11 of 140 (7.85%) patients and PCR was positive in 3 of 140 (2.14%) patients. Culture was negative in all the cases. A higher incidence of Bartonella infection was seen in patients with fever and lymphadenopathy (n=30), seven of whom were children. In ophthalmological conditions, four cases were IFA positive. INTERPRETATION & CONCLUSIONS: The present study shows that the threat of Bartonella infection is a reality in India. It is also an important treatable cause of fever and lymphadenopathy in children. Serology and PCR are useful tests for its diagnosis. Clinicians should consider. BARTONELLA: infection in the differential diagnosis of febrile illnesses and chronic diseases.

Nagging Presence of Clostridium difficile Associated Diarrhoea in North India.

INTRODUCTION: Clostridium Difficile Associated Diarrhoea (CDAD) is a significant cause of morbidity in hospitalised patients worldwide. The data on clinical epidemiology of this disease in Indian subcontinent is scarce. AIM: To evaluate the risk factors and clinical course of patients with CDAD. MATERIALS AND METHODS: A cross-sectional study was planned at our tertiary care centre, All India Institute of Medical Sciences, whereby, all patients who had nosocomial diarrhea between 2010 and 2014 were included in the study. Their clinical and laboratory profile were recorded using structured questionnaire and their stool samples were subjected to ELISA for detection of toxins A and B (Premier toxins A and B). Those patients who had toxins A and B in their stool samples were diagnosed as CDAD. The clinical and laboratory profile of CDAD patients were further analysed. RESULTS: A total of 791 patients with nosocomial diarrhea were included in this study. CDAD was diagnosed in a total of 48(6%) patients. The year wise breakdown of the positive patients is as follows: 7/135 (5.2%), 4/156 (2.6%), 5/141 (3.5%), 9/193 (4.7%) and 23/166 (13.8%), respectively. A total of 16/48 (33.3%) of CDAD cases belonged to the age group of 51-60 years. Malignancy (n=15, 31.25%) was the most common underlying pathological condition. All the patients had a history of antibiotic intake. Most common antibiotic used in the patients of CDAD was third generation cephalosporins (n=27, 56.25%). The use of clindamycin, carbapenems and colistin increased in the year 2014. Mean duration of hospital stay was 9.8 days. Diarrhoea was associated with fever in 50% of the patients while abdominal pain was seen in 39.6% of the patients. CONCLUSION: The control of Clostridium difficile infection suffers from the rampant use of higher antibiotics. There is a need for proper implementation of antimicrobial stewardship programmes and better hospital infection control to stop the transmission of this nagging bug.

Varied presentations of leptospirosis: experience from a tertiary care hospital in north India.

Leptospirosis has been recognised as an emerging global public health problem. The aim of our study was to explore the epidemiological and clinical pattern of disease occurrence in suspected cases and to search for any existing co-infections. Ours was a retrospective study in patients with acute febrile illness in north India over a period of three years (April 2011 to June 2014). Serological diagnosis of leptospirosis was made using the PanBio IgM ELISA kit. Using modified Faine's criteria, presumptive and possible diagnosis was made in 57% and 34% cases, respectively. Most of the affected population was resident in north and central India. Nineteen patients showed co-infection with other common pathogens prevailing locally. There is a need to increase awareness and understand the local sero-epidemiological pattern of leptospirosis so that timely preventive and curative action may be taken by healthcare authorities.

Clostridium sordellii as a cause of constrictive pericarditis with pyopericardium and tamponade.

Systemic infections caused by Clostridium sordellii are rare. They are usually reported in cases of skin and soft tissue infections and sometimes in cases of toxic shock syndrome involving exotoxins. We report here the first case of Clostridium sordellii infection associated with acute constrictive pericarditis and with pyopericardium and tamponade.