Neuroimmunomodulation by gut bacteria: Focus on inflammatory bowel diseases.

Microbes colonize the gastrointestinal tract are considered as highest complex ecosystem because of having diverse bacterial species and 150 times more genes as compared to the human genome. Imbalance or dysbiosis in gut bacteria can cause dysregulation in gut homeostasis that subsequently activates the immune system, which leads to the development of inflammatory bowel disease (IBD). Neuromediators, including both neurotransmitters and neuropeptides, may contribute to the development of aberrant immune response. They are emerging as a regulator of inflammatory processes and play a key role in various autoimmune and inflammatory diseases. Neuromediators may influence immune cell's function via the receptors present on these cells. The cytokines secreted by the immune cells, in turn, regulate the neuronal functions by binding with their receptors present on sensory neurons. This bidirectional communication of the enteric nervous system and the enteric immune system is involved in regulating the magnitude of inflammatory pathways. Alterations in gut bacteria influence the level of neuromediators in the colon, which may affect the gastrointestinal inflammation in a disease condition. Changed neuromediators concentration via dysbiosis in gut microbiota is one of the novel approaches to understand the pathogenesis of IBD. In this article, we reviewed the existing knowledge on the role of neuromediators governing the pathogenesis of IBD, focusing on the reciprocal relationship among the gut microbiota, neuromediators, and host immunity. Understanding the neuromediators and host-microbiota interactions would give a better insight in to the disease pathophysiology and help in developing the new therapeutic approaches for the disease.

Forest malaria: the prevailing obstacle for malaria control and elimination in India.

Despite the decrease in malaria mortality and morbidity, it remains a significant public health problem in India. India is targeting malaria elimination from the country by 2030. Different areas in India are in different phases of malaria elimination. The emerging resistance in vectors as well parasite have added necessity to accelerate the malaria elimination programme. Forested areas remain the foci for malaria transmission due to favourable human and environmental factors. Here, we analysed the longitudinal data from 2000 to 2019 to see the trends in forest malaria in India. Population living in forested areas are major malaria contributors. From 2000 to 2019, ~32% of malaria cases and 42% of malaria related deaths were reported from forested districts which represent only ~6.6% of the total Indian population. Increasing insecticide resistance, a high percentage of submicroscopic infections and challenging to test and treat communities are the crucial components of the prevailing obstacles of forested malaria. To achieve the elimination goal, efforts should be intensified with more resources diverted to the forested areas. Malaria control in forested areas will bring fruitful results for malaria control in India.

Knowledge Attitude and Practices of Mitanin's (Community Health Workers) in Chhattisgarh: Malaria Elimination Perspective.

Background: For the success of any program, its implementation plays a crucial role. Community health workers are of immense importance for malaria elimination from India. Objective: This study was aimed to assess the knowledge gaps and the responsible factors for mitanins' knowledge on various aspects of and problems faced by mitanins during their work. Methods: Structured interviewer-based questionnaire was used to collect the data, and ordinal regression was applied to analyze the data. Results: Only 26% of the mitanins were having a good knowledge attitude and practices (KAP) score about malaria. Malaria endemicity of area [odds ratio (OR) = 0.26, 95% CI = 0.13-0.50), P < 0.001] and education (OR = 0.35, 95% CI = 0.18-0.69, P = 0.002) were the two significant factors affecting the KAP of mitanins. Conclusion: This study shows that prioritizing education while recruiting the mitanins and training them in the low endemic areas with a focus on malaria, which will help achieve the malaria elimination goal.

Correction: Association of miR-196a-2 and miR-499 variants with ulcerative colitis and their correlation with expression of respective miRNAs.

[This corrects the article DOI: 10.1371/journal.pone.0173447.].

Association of miR-196a-2 and miR-499 variants with ulcerative colitis and their correlation with expression of respective miRNAs.

BACKGROUND AND AIM: MicroRNAs are small non-coding RNAs that play an important role in regulating the gene expression of their target genes. SNP miR-196a-2 rs11614913 and miR-499 rs3746444 are reported to have association with the risk and prognosis of multiple-types of inflammatory diseases including IBD. This study was conducted to show if any association of SNP miR-196a-2rs11614913 and miR-499 rs3746444 exists with ulcerative colitis (UC) patients of north Indian population and how these polymorphisms modulate the expression profile of the respective miRNAs. METHODS: A total of 638 participants including 197 UC patients and 441 controls were included in this study. Polymorphisms were genotyped by PCR-RFLP and the miRNA expression was measured using qRT-PCR. Genotypes and allele frequencies were calculated using SPSS 16 software. RESULTS: MiR-196a-2 rs11614913 (C>T) and miR-499 rs3746444 (T>C) were found to be associated with UC. TT genotype of miR-196a-2 rs11614913 (p = 0.03) was negatively associated with UC whereas the heterozygous TC genotype of miR-499 rs3746444 (p = 0.003) was showing positive association with UC. Patients having a combination of both SNPs, developed disease at older age and they suffered from severe disease extent. Genotype that showed association with the disease also showed correlation with the changes in miRNA expression. CONCLUSION: In this study we found miR-196a-2 rs11614913 and miR-499 rs3746444 were associated with UC in north Indian population. We found the genotype that showed association with UC also altered the expression of respective miRNA in the patient harboring the genotype. There was correlation between associated genotype and altered miRNA expression.

Site-Specific MicroRNA Expression May Lead to Different Subtypes in Ulcerative Colitis.

BACKGROUND AND AIM: Ulcerative Colitis (UC) is a type of inflammatory bowel disease, considered as an important disease of gastrointestinal tract having a huge impact on the health of the patient. Prolonged inflammation of colon in UC patients increases the risk of developing colorectal cancer. MiRNA are reported as a connecting link between inflammation and cancer. Differential miRNA expression is reported in Crohn's disease (CD) patients involving various regions of the gastrointestinal tract. The current study was performed to dissect out the site specific miRNA expression in the colon biopsy samples of UC patients from Northern India. METHODS: Biopsy samples were collected from UC patients and healthy controls from Rectosigmoid Area (RS) and Ascending Colon (AC). MiRNA expression was compared between patients with RS and AC using a microarray platform. Differential expression was further validated by Real Time PCR analysis. Demographic and pathological data of UC -associated CRC patients was collected from the hospital database and analyzed for assessing the site of cancer. RESULTS: Upon analysis of data generated on a microarray platform and qRT PCR revealed that the expression of six miRNAs hsa-miR-146b-5p, hsa-miR-335-3p, hsa-miR-342-3p, hsa-miR-644b-3p, hsa-miR-491-3p, hsa-miR-4732-3p were downregulated in patients where RS was involved as compared to AC. The expression of hsa-miR-141-3p was upregulated in patients where RS region was involved as compared to AC. Analysis of the registered UC patient's database from the hospital revealed that the site of CRC was predomimnantly the rectosigmoid region of the colon in most of the cases. CONCLUSION: This is the first study to show the differential expression of miRNA involving different sites of colon in UC patients. Taking our data and previous reports into consideration, we propose that differential miRNA expression during UC perhaps contribute in the development of UC-associated CRC at the rectosigmoid area.

Effect of salicin on gut inflammation and on selected groups of gut microbiota in dextran sodium sulfate induced mouse model of colitis.

OBJECTIVE AND DESIGN: This study was undertaken to evaluate the anti-inflammatory effect of the pure compound salicin on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to quantify the major gut bacteria during the treatment. MATERIAL OR SUBJECTS: Experimental colitis was induced in Swiss albino mice by dissolving 2 % DSS in their drinking water for 7 days. Five mice were used in each group. TREATMENT: Salicin (100 and 200 mg per body weight) was administered daily through oral gavage for 7 days. METHODS: Disease activity index (DAI), colon length, myeloperoxidase (MPO) assay, pro-inflammatory cytokine expression, histological changes and absolute number of gut microbiota were measured after treatment. Student's t test was applied for statistical analysis. RESULTS: Salicin significantly attenuated DSS-induced DAI scores, shortening of colon length and tissue MPO activity. Salicin administration also effectively and dose-dependently prevented pro-inflammatory cytokine expression in DSS-induced colitis mice. Histological examination indicated that salicin suppressed edema, mucosal damage and the loss of crypts induced by DSS. Oral administration of salicin in DSS-treated mice prevented loss of gut microbiota during the short period of treatment. CONCLUSIONS: Salicin has an anti-inflammatory effect, and it may have therapeutic value in ameliorating inflammation during colitis.