The effects of global warming are not limited to rising global temperatures and have set in motion a complex chain of events contributing to climate change. A consequence of global warming and the resultant climate change is the rise in cyanobacterial harmful algal blooms (cyano-HABs) across the world, which pose a threat to public health, aquatic biodiversity, and the livelihood of communities that depend on these water systems, such as farmers and fishers. An increase in cyano-HABs and their intensity is associated with an increase in the leakage of cyanotoxins. Microcystins (MCs) are hepatotoxins produced by some cyanobacterial species, and their organ toxicology has been extensively studied. Recent mouse studies suggest that MCs can induce gut resistome changes. Opportunistic pathogens such as Vibrios are abundantly found in the same habitat as phytoplankton, such as cyanobacteria. Further, MCs can complicate human disorders such as heat stress, cardiovascular diseases, type II diabetes, and non-alcoholic fatty liver disease. Firstly, this review describes how climate change mediates the rise in cyanobacterial harmful algal blooms in freshwater, causing increased levels of MCs. In the later sections, we aim to untangle the ways in which MCs can impact various public health concerns, either solely or in combination with other factors resulting from climate change. In conclusion, this review helps researchers understand the multiple challenges brought forth by a changing climate and the complex relationships between microcystin, Vibrios, and various environmental factors and their effect on human health and disease.

Epidemiological studies have reported a strong association between liver injury and incidences of hepatocellular carcinoma in sections of humans globally. Several preclinical studies have shown a strong link between cyanotoxin exposure and the development of nonalcoholic steatohepatitis, a precursor of hepatocellular carcinoma. Among the emerging threats from cyanotoxins, new evidence shows cylindrospermopsin release in freshwater lakes. A known hepatotoxin in higher concentrations, we examined the possible role of cylindrospermopsin in causing host gut dysbiosis and its association with liver pathology in a mouse model of toxico-pharmacokinetics and hepatic pathology. The results showed that oral exposure to cylindrospermopsin caused decreased diversity of gut bacteria phyla accompanied by an increased abundance of Clostridioides difficile and decreased abundance of probiotic flora such as Roseburia, Akkermanssia, and Bacteroides thetaiotamicron, a signature most often associated with intestinal and hepatic pathology and underlying gastrointestinal disease. The altered gut dysbiosis was also associated with increased Claudin2 protein in the intestinal lumen, a marker of gut leaching and endotoxemia. The study of liver pathology showed marked liver inflammation, the release of damage-associated molecular patterns, and activation of toll-like receptors, a hallmark of consistent and progressive liver damage. Hepatic pathology was also linked to increased Kupffer cell activation and stellate cell activation, markers of progressive liver damage often linked to the development of liver fibrosis and carcinoma. In conclusion, the present study provides additional evidence of cylindrospermopsin-linked progressive liver pathology that may be very well-linked to gut dysbiosis, though definitive evidence involving this link needs to be studied further.

The pathophysiology of Gulf War Illness (GWI) remains elusive even after three decades. The persistence of multiple complex symptoms along with metabolic disorders such as obesity worsens the health of present Gulf War (GW) Veterans often by the interactions of the host gut microbiome and inflammatory mediators. In this study, we hypothesized that the administration of a Western diet might alter the host metabolomic profile, which is likely associated with the altered bacterial species. Using a five-month symptom persistence GWI model in mice and whole-genome sequencing, we characterized the species-level dysbiosis and global metabolomics, along with heterogenous co-occurrence network analysis, to study the bacteriome–metabolomic association. Microbial analysis at the species level showed a significant alteration of beneficial bacterial species. The beta diversity of the global metabolomic profile showed distinct clustering due to the Western diet, along with the alteration of metabolites associated with lipid, amino acid, nucleotide, vitamin, and xenobiotic metabolism pathways. Network analysis showed novel associations of gut bacterial species with metabolites and biochemical pathways that could be used as biomarkers or therapeutic targets to ameliorate symptom persistence in GW Veterans.