Gut microbes shape microglia and cognitive function during malnutrition.

Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood-brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target.

Dynamics of expression, secretion and translocation of type III effectors during enteropathogenic Escherichia coli infection.

Enteropathogenic Escherichia coli (EPEC) is an important cause of infant diarrhea and mortality worldwide. The locus of enterocyte effacement (LEE) pathogenicity island in the EPEC genome encodes a type 3 secretion system (T3SS). This nanomachine directly injects a sophisticated arsenal of effectors into host cells, which is critical for EPEC pathogenesis. To colonize the gut mucosa, EPEC alters its gene expression in response to host environmental signals. Regulation of the LEE has been studied extensively, revealing key mechanisms of transcriptional regulation, and more recently at the posttranscriptional and posttranslational levels. Moreover, the T3SS assembly and secretion is a highly coordinated process that ensures hierarchical delivery of effectors upon cell contact. EPEC effectors and virulence factors not only manipulate host cellular processes, but also modulate effector translocation by controlling T3SS formation. In this review, we focus on the regulation of EPEC virulence genes and modulation of effector secretion and translocation.

The Gut Microbiota-Brain Axis Expands Neurologic Function: A Nervous Rapport.

Does exploration of the gut microbiota-brain axis expand our understanding of what it means to be human? Recognition and conceptualization of a gut microbiota-brain axis challenges our study of the nervous system. Here, integrating gut microbiota-brain research into the metaorganism model is proposed. The metaorganism-an expanded, dynamic unit comprising the host and commensal organisms-asserts a radical blurring between man and microbe. The metaorganism nervous system interacts with the exterior world through microbial-colored lenses. Ongoing studies have reported that gut microbes contribute to brain function and pathologies, even shaping higher neurological functions. How will continued collaborative efforts (e.g., between neurobiology and microbiology), including partnerships with the arts (e.g., philosophy), contribute to the knowledge of microbe-to-mind interactions? While this is not a systemic review, this nascent field is briefly described, highlighting ongoing challenges and recommendations for emerging gut microbiota-brain research. Also see the video abstract here https://youtu.be/lP9gOW8StXg.

The commensal microbiota drives immune homeostasis.

For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.