ABSTRACT
The human gut microbiota creates a complex microbial ecosystem, characterized by its high population density, wide diversity, and complex interactions. Any imbalance of the intestinal microbiome, whether qualitative or quantitative, may have serious consequences for human health, including small intestinal bacterial overgrowth (SIBO). SIBO is defined as an increase in the number of bacteria (103-105 CFU/mL), an alteration in the bacterial composition, or both in the small intestine. The PubMed, Science Direct, Web of Science, EMBASE, and Medline databases were searched for studies on SIBO and related diseases. These diseases were divided into 12 groups: (1) gastrointestinal disorders; (2) autoimmune disease; (3) cardiovascular system disease; (4) metabolic disease; (5) endocrine disorders; (6) nephrological disorders; (7) dermatological diseases; (8) neurological diseases (9); developmental disorders; (10) mental disorders; (11) genetic diseases; and (12) gastrointestinal cancer. The purpose of this comprehensive review is to present the current state of knowledge on the relationships between SIBO and these 12 disease groups, taking into account risk factors and the causal context. This review fills the evidence gap on SIBO and presents a biological-medical approach to the problem, clearly showing the groups and diseases having a proven relationship with SIBO, as well as indicating groups within which research should continue to be expanded.
ABSTRACT
Receptor tyrosine kinase inhibitors have been a standard first-line therapy for renal cell carcinoma (RCC) for over a decade. Although they stabilize the disease, they are unable to remove all tumor cells, leading to relapse. Moreover, both intrinsic and acquired resistance to therapy are a significant health burden. In order to overcome resistance, several combination therapies have been recently approved by the FDA. Another approach takes advantage of altered metabolism in tumor cells, which switch to alternative metabolic pathways to sustain their rapid growth and proliferation. CB-839 is a small molecule inhibitor of kidney type glutaminase (GLS). GLS is often upregulated in glutamine addicted cancers, enhancing glutamine metabolism for the production of energy and the biosynthesis of various cellular building blocks. CB-839 is currently in clinical trials for several tumors, including clear cell (cc)RCC, both as monotherapy and in combination with the approved therapeutic agents everolimus, cabozantinib and nivolumab. Early results of Phase 1/2 clinical trials look promising, especially for CB-839 plus cabozantinib, and all combinations seem to be well tolerated. However, cancer cells can activate compensatory pathways to overcome glutaminolysis inhibition. Therefore, genetic and metabolomic studies are crucial for the successful implementation of CB-839 alone or in combination in subgroups of ccRCC patients.
