Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis.

Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis via the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field.

Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa.

BACKGROUND: Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN. METHODS: We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study. RESULTS: The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0-622) pg/mgCr from a baseline of 1092.7 (IQR 578.6-1848) pg/mgCr (P = 0.06) while uTWEAK had reduced to 36.0 (IQR 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P = 0.03). For patients reaching early complete or partial remission (n = 17), both biomarkers had significantly declined in their urine: uMCP-1 (P = 0.018) and uTWEAK (P = 0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features. CONCLUSION: Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can, therefore, be useful for monitoring disease activity and treatment response.