Role of the Microbiome in Gut-Heart-Kidney Cross Talk

Abstract

Homeostasis is a prerequisite for health. When homeostasis becomes disrupted, dysfunction occurs. This is especially the case for the gut microbiota, which under normal conditions lives in symbiosis with the host. As there are as many microbial cells in and on our body as human cells, it is unlikely they would not contribute to health or disease. The gut bacterial metabolism generates numerous beneficial metabolites but also uremic toxins and their precursors, which are transported into the circulation. Barrier function in the intestine, the heart, and the kidneys regulates metabolite transport and concentration and plays a role in inter-organ and inter-organism communication via small molecules. This communication is analyzed from the perspective of the remote sensing and signaling theory, which emphasizes the role of a large network of multispecific, oligospecific, and monospecific transporters and enzymes in regulating small-molecule homeostasis. The theory provides a systems biology framework for understanding organ cross talk and microbe-host communication involving metabolites, signaling molecules, nutrients, antioxidants, and uremic toxins. This remote small-molecule communication is critical for maintenance of homeostasis along the gut-heart-kidney axis and for responding to homeostatic perturbations. Chronic kidney disease is characterized by gut dysbiosis and accumulation of toxic metabolites. This slowly impacts the body, affecting the cardiovascular system and contributing to the progression of kidney dysfunction, which in its turn influences the gut microbiota. Preserving gut homeostasis and barrier functions or restoring gut dysbiosis and dysfunction could be a minimally invasive way to improve patient outcomes and quality of life in many diseases, including cardiovascular and kidney disease.

The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders

“…The host's outer and inner surfaces such as skin or gastrointestinal epithelia are densely inhabited by microorganisms, and the human microbiome in the gut comprises an impressive number and diversity of microorganisms with numerous co-evolutionary associations . Due to the co-evolution of host and microbiota, symbiotic relationships have evolved, in which the bidirectional interactions between the host and their microflora influence health and disease, for example by impacting host energy, lipid and carbohydrate homeostasis as well as the physiology of organs like kidney, liver, heart or brain (see Sekirov et al, 2010;Cani and Knauf, 2016;Adolph et al, 2018;Stavropoulou et al, 2020;Zheng and Wang, 2021;Shahab and Shahab, 2022;Glorieux et al, 2023;Hsu and Schnabl, 2023;Nesci et al, 2023). Bacterial colonization of the gastrointestinal (GI) tract plays a dominant role in processes of human post-natal development and maturation of the immune, endocrine, and central nervous systems (CNS) (Afzal et al, 2020;Banfi et al, 2021;Hill et al, 2021;Ahmed et al, 2022;Yousefi et al, 2022;Sasso et al, 2023;Van Pee et al, 2023).…”

Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

“…Moreover, the gut microbiota composition of patients with CKD differs significantly from that of healthy individuals, and changes in gut microbiota composition may indicate CKD severity or progression. [34] Therefore, further exploration of the gut microbiota is crucial for understanding the mechanisms underlying CKD and developing effective therapeutic strategies. Bibliometric analysis is an effective and feasible method for understanding research trends and focal areas within a given field, ultimately aiding researchers and clinicians in shaping future investigations and clinical treatments.…”

Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease

“…208,209 Several microbe-derived metabolites act as uremic toxins, including TMAO and IPA, in addition to other protein-derived metabolites. 210,211 Communication between the host and microbial metabolism can occur at any point throughout the lifetime but may be particularly important during early life. As mentioned earlier, the evidence supporting prenatal microbial colonization is limited.…”