L-Ascorbic Acid Restricts Vibrio cholerae Survival in Various Growth Conditions.

Cholera, a deadly diarrheal disease, continues to ravage various parts of the world. It is caused by Vibrio cholerae, an important member of the gamma-proteobacteria. Based on certain genetic and phenotypic tests, the organism is classified into two major biotypes, namely classical and El Tor. The El Tor and its variants are majorly responsible for the ongoing seventh pandemic across the globe. Previously, we have shown that cross-feeding of glucose metabolic acidic by-products of gut commensals can severely affect the viability of the biotypes. In this work, we examined the effect of L-ascorbic acid on the survival of Vibrio cholerae strains belonging to both biotypes and different serotypes. We observed that L-ascorbic acid effectively restricts the growth of all strains under various conditions including strains adapted to acid stress. In addition, L-ascorbic acid is also effective in decreasing bile-induced biofilms of Vibrio cholerae.

Chemically Defined Lactobacillus plantarum Cell-Free Metabolites Demonstrate Cytoprotection in HepG2 Cells through Nrf2-Dependent Mechanism.

Centering around the concept that metabolites from the gut commensals can exert metabolic health benefits along the gut-liver axis, we tested whether the cell-free global metabolome of probiotic bacteria can exert hepatoprotective benefits against H2O2-induced oxidative stress. Cell-free global metabolites of Lactobacillus plantarum (LPM) were isolated and untargeted metabolomics was performed. The free radical scavenging potentials of LPM were measured. The cytoprotective effects of LPM were tested on HepG2 cells. A total of 66 diverse metabolites were identified in LPM, among which saturated fatty acids, amino acids and dicarboxylic acids were highly enriched. LPM attenuated cell damage, lipid peroxidation and the levels of intracellular cytoprotective enzymes in H2O2-treated cells. LPM also attenuated H2O2-induced increased expressions of TNF-α and IL-6. However, the cytoprotective effects of LPM were diminished in cells that were pretreated with a pharmacological inhibitor of Nrf2. Our data collectively indicate that LPM can significantly attenuate oxidative damage to HepG2 cells. However, the cytoprotective effects of LPM likely depend on an Nrf2-dependent mechanism.

The opportunistic nature of gut commensal microbiota.

The abundance of gut commensals has historically been associated with health-promoting effects despite the fact that the definition of good or bad microbiota remains condition-specific. The beneficial or pathogenic nature of microbiota is generally dictated by the dimensions of host-microbiota and microbe-microbe interactions. With the increasing popularity of gut microbiota in human health and disease, emerging evidence suggests opportunistic infections promoted by those gut bacteria that are generally considered beneficial. Therefore, the current review deals with the opportunistic nature of the gut commensals and aims to summarise the concepts behind the occasional commensal-to-pathogenic transformation of the gut microbes. Specifically, relevant clinical and experimental studies have been discussed on the overgrowth and bacteraemia caused by commensals. Three key processes and their underlying mechanisms have been summarised to be responsible for the opportunistic nature of commensals, viz. improved colonisation fitness that is dictated by commensal-pathogen interactions and availability of preferred nutrients; pathoadaptive mutations that can trigger the commensal-to-pathogen transformation; and evasion of host immune response as a survival and proliferation strategy of the microbes. Collectively, this review provides an updated concept summary on the underlying mechanisms of disease causative events driven by gut commensal bacteria.

Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches.

Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.