Round up of research articles published between 1st – 31st July 2023 by CSIR-IGIB:
Extracellular vesicles and inflammatory diseases
Inflammation is seen as a cause and effect of various chronic diseases like Chronic Obstructive Pulmonary Disease (COPD), atherosclerosis, and neurodegenerative disorders. Cell death is a hallmark of all these diseases, which can worsen with prolonged inflammation, leading to necrosis and tissue damage. The delayed clearance of apoptotic cells can further exacerbate tissue damage. The apoptotic cells are cleared by macrophages in a process called efferocytosis, which has been observed to be impaired in chronic inflammatory diseases.
As apoptotic cells are engulfed by macrophages, soluble signaling molecules and extracellular vesicles (EVs) are released, which help in controlling inflammation via intercellular signaling. Although, many studies have elucidated the mediators of inflammation released by macrophages after engulfment of apoptotic cells, the role of EVs (that also release various signaling molecules like proteins, mRNA, and long non coding RNAs) in regulating macrophages is yet to be explored.
In this study, Manikanandan Subramanian (former scientist at CSIR-IGIB) and Shantanu Sengupta’s labs have identified the signaling pathway that plays a role in modulating macrophages for and after efferocytosis. They showed that the signaling molecules contained and released by the EVs (released by the macrophages after the engulfment of apoptotic cells) can further potentiate the nearby (naive) macrophages to engulf apoptotic cells. These EVs and their signaling molecules thus help in faster clearance leading to halting of inflammation and further progression of tissue injury. They corroborated these findings in an animal model of atherosclerosis. Further studies would help in developing therapeutic strategies for slowing down the progression of chronic inflammatory diseases.
Hyperglycemia and the microbiota of the upper gut
Having recognized the role of gut microbiota in diabetes by various research groups, in this study we have focused on hyperglycemia, a condition which precedes diabetes and often goes undiagnosed but presents a unique opportunity to understand the early effects of disease on biological health of humans.
Though the estimates of microbial to human cells has been revised, but to date 10% humans still remains a popular belief. There are 3.3 million bacterial genes that complement 20,000 genes of human and gut constitute the largest niche of microbes. Though, microbiome research has heavily relied on stool samples for studying gut bacterial profile, however they reflect the microbiota resembling the distal gut and fail to provide information about the mucosa associated microbiota, that closely interacts with the host in the upper gut. So, the question arises, what is the relationship between upper gut, particularly duodenum, and glycemia.
Well, the conventional role of duodenum in nutrient sensing and absorption as well as its crosstalk with pancreas via the entero-insular axis releasing GLP-1, GIP that stimulates insulin secretion from pancreas is well established. Recently, various duodenal exclusion and resurfacing studies have shown improvement in metabolic profile, such as significant drop in the levels of HbA1c. Overall, existing evidence around the role of duodenum in diabetes is focused on local nutrient effects via the gut hormonal axis, but indirect effects through dysbiosis and immune stimulation are plausible. For example, one of the mechanisms by which glucoregulatory action of metformin drug is elicited is via alteration of small intestinal microbiota. Furthermore, another drug that improves insulin sensitivity is resveratrol that activates duodenal specific Sirt1.
With this background, we hypothesized that the Duodenum bacterial dysbiosis and the altered microenvironment may be associated with hyperglycemia. This work was a collaborated effort of IGIB, and PGIMER, where Aarti Darra, PhD student of Dr Anurag Agrawal, co-supervised by Dr Usha Dutta, Head and Prof. Dept. of Gastroenterology, undertook this study.
The results of the study showed that less perfused duodenum with increased bacteria in a pro-inflammatory state is experiencing altered motility and is linked to hyperglycemia. Unlike stool microbiome, variability in the duodenal MAM profile showed association with glycemia. Hyperglycemic group showed a lower abundance of enzymes belonging to aromatic amino acid biosynthesis and of TCA cycle pathway and pathways of purine/pyrimidine metabolism and translation were elevated in hyperglycemic group. As a conclusion, assessment of small intestinal mucosa associated microbiota, with the inclusion of a quantitative approach, merits deeper investigation as a health determinant.
Aarti Darra is a researcher who finds people to be beautiful experiments. She writes to woo herself.