Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression

Abstract

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches.

The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease

“…Increased CKD, increased cardiovascular risk, uremic toxicity, and inflammation are associated with modifications to the microbiota and the subsequent diverse host responses (85). Experimental and clinical data from genomic and nongenomic studies have suggested that an unusual composition of microbiota exists in CKD (7), and preliminary results have suggested that the composition of the microbiota in chronic renal failure patients and early stages of CKD may be altered (87). More recently, the accumulation of uremic toxins was shown to be due to a number of microbiota strains.…”

“…Many uremic toxins are derived from the absorption of nutrients by gut microbiota, as these nutrients enhance bacterial growth, which in turn produce more uremic toxins. Thus, possible treatments can involve diet modification, changes in microbiota, reducing the production of uremic toxins by microbiota, increasing the excretion of toxins or targeting the removal of certain uremic toxins (7). Of these, diet is the most powerful and easily controlled factor in intestinal microbiota modulation.…”

“…A higher intake of certain nutrients may also affect the intestinal microbiota, and lead to the increased bacterial production of uremic toxins or precursors. Thus, circulating concentrations of nutrient-derived uremic contaminants are associated with an increased risk of CKD development (7).…”

Kidneys and microbiota

“…Изучение экологического разнообразия микробного сообщества, согласно индексам альфа-разнообразия Шеннона, показало, что по сравнению со здоровыми лицами, при ХБП на уровне типа увеличено количество протеобактерий, снижено количество фирмикут и актинобактерий, на уровне семейства отмечено увеличение энтеро-и коринобактерий, на уровне рода возрастает количество энтерококков и клостридий. При ХБП доказан повышенный риск прогрессирования болезни при снижении экспрессии генов, связанных с метаболизмом холина, бетаина, L-карнитина, триметиламина-N-оксида (ТМАО) [27].…”

“…После трансплантации почки содержание полиаминов в сыворотке крови уменьшается в 3-5 раз [37]. Экспериментальные и клинические исследования, геномные и негеномные, подтвердили развитие дисбиоза при ХБП [27]. Специфические уремические токсины (ТМАО, р-крезол сульфат (PCS), р-крезол глюконид (PCG), индоксил-сульфат (IS), индол-3 ацетоуксусной кислоты (IA), вит.…”