The human gut microbiota can be potentially disrupted due to exposure of various environmental contaminants, including pesticides. These contaminants enter into non-target species in multiple ways and cause potential health risks. The gut microbiota-derived metabolites have a significant role in maintaining the host’s health by regulating metabolic homeostasis. An imbalance in this homeostasis can result in the development of various diseases and their pathogenesis. Pesticides have hazardous effects on the host’s gut microbiota, which is evident in a few recent studies. Therefore, there is an urgent need to explore the effect of pesticide on gut microbiota-mediated metabolic changes in the host, which may provide a better understanding of pesticide-induced toxicity. The present review summarizes the pesticide-induced effects on gut microbiota, which in turn, induces changes in the release of their secondary metabolites that could lead to various host health effects.

The marine environment has a remarkable source of natural products mainly from marine fungi, which have been a central source of novel pharmacologically bioactive secondary metabolites. In this study, the search for a new potential apoptosis-inducing metabolite is focused on marine sponge-associated symbionts. A total of sixteen different sponges were obtained from the Gulf of Mannar region, India, and twenty-three different marine fungal strains were isolated and tested for antiproliferative activity by the MTT assay. Out of these, Monascus sp. NMK7 associated with the marine sponge Clathria frondifera was found to have a promising antiproliferative property. Furthermore, to isolate the pure active metabolite, the crude material was subjected to column chromatography and HPLC. Structural characterization was conducted by a variety of spectroscopic techniques including UV, IR, MS and NMR. The obtained results from the MS and NMR spectroscopy determined 418.5 Da to be the molecular weight and C₂₄H₃₄O₆ to be the molecular formula of the metabolite, indicating the presence of monacolin X (NMKD7). NMKD7 was found to induce dose-dependent cytotoxicity in different human breast cancer cell lines MCF-7, T47D, MDA-MB-231, MDA-MB-468 and MCF-10A normal breast cell after 24 h of exposure. For elucidating the possible mode of cell death, T47D and MDA-MB-468 cells were treated with NMKD7 for 24 h to examine the morphological change of the chromatin (PI & AO/EB). Therefore, it has been suggested as the possible mechanism of apoptosis, and apart from this, it has also exhibited antibacterial and anti-migratory properties as well as induced the ROS stress (DCFH-DA), which causes the mitochondrial membrane potential difference (Rhodamine-123), the loss of cell membrane integrity and eventually cell death. Thus, the present study features a novel promising apoptosis-inducing metabolite (NMKD7) with minimal toxicity, suggesting its potential for biotechnological applications, and substantiates that it should be further considered for the elucidation of molecular targets and signal transduction pathways.

Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J mice, we evaluated RCJ’s protective role in DSS-induced colitis through two cycles of 3% DSS. Mice were daily gavaged with PBS or RCJ until the endpoint, and gut microbiota composition was analyzed via shotgun metagenomics. RCJ treatment significantly improved body weight (p ≤ 0.001), survival in mice (p < 0.001) and reduced disease activity index (DAI) scores. Further, RCJ improved colonic barrier integrity by enhancing the expression of protective colonic mucins (p < 0.001) and tight junction proteins (p ≤ 0.01) in RCJ + DSS-treated mice compared to the DSS group. Shotgun metagenomic analysis revealed an enrichment of short-chain fatty acids (SCFAs)-producing bacteria (p < 0.05), leading to increased Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) activation (p ≤ 0.001). This, in turn, resulted in repression of the nuclear factor κB (NFκB) signaling pathway, causing decreased production of inflammatory cytokines and chemokines. Our study demonstrates colitis remission in a DSS-induced mouse model, showcasing RCJ as a potential modulator for gut microbiota and metabolites, with promising implications for IBD prevention and treatment.