Alteration of the Gut Microbiome in Chronic Kidney Disease Patients and Its Association With Serum Free Immunoglobulin Light Chains

Abstract

ObjectivesGut dysbiosis is associated with chronic kidney disease (CKD), and serum free immunoglobulin light chains (FLCs) are biomarkers for CKD. This study aims to assess the CKD gut microbiome and to determine its impact on serum FLC levels.MethodsTo control for confounders, 100 patients and sex- and age-matched healthy controls (HCs) were recruited. The gut microbiome was assessed by sequencing 16S rRNA gene V3-V4 hypervariable regions. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was applied to infer functional metabolic pathways. When observing group differences in the microbiome and predicted metabolic pathways, demographic confounders were adjusted using binary logistic regression; when examining impacts of the gut microbiome and metabolic pathways on serum FLCs, factors influencing FLC levels were adjusted using multiple regression.ResultsPrincipal coordinate analysis revealed a significantly different bacterial community between the CKD and HC groups (P < 0.05). After adjusting for confounders, lower Chao 1, observed species and Shannon indices based on binary logistic regression predicted CKD prevalence. Actinobacteria, Alistipes, Bifidobacterium and Bifidobacterium longum enrichment, upregulation of metabolic pathways of bacterial toxin, chloroalkane and chloroalkene degradation, and Staphylococcus aureus infection also predicted CKD prevalence (P < 0.05). Furthermore, depletion of Actinobacteria and Bifidobacterium and reduced chloroalkane and chloroalkene degradation predicted high levels of FLC λ (P < 0.05).ConclusionsGut dysbiosis in CKD patients was confirmed by controlling for confounders in the present study. Additionally, the association between gut dysbiosis and FLC λ levels demonstrates the existence of crosstalk between the microbiome and immune response in CKD.

Gut Mycobiome in Patients With Chronic Kidney Disease Was Altered and Associated With Immunological Profiles

“…The CKD patients with normal or high eGFR, moderate CKD, and end-stage CKD displayed a different fungal community with respect to healthy subjects, whereas the patients with mild CKD and severe CKD did not exhibit a difference from that in the HC cohort. These findings also appeared in our previous study on the bacterial microbiome in CKD patients ( 3 ). The restoring process that appeared in patients, including the fungal and bacterial microbiome, should be examined using animal models.…”

“…As sex, age, and BMI are important variables affecting the gut microbiome ( 23 – 25 ), we recruited ninety-two CKD patients and sex–age–BMI–matched healthy controls (HCs) were recruited from December 2018 to February 2020. The inclusion and exclusion criteria were based on our recent study on the bacterial microbiome in CKD patients ( 3 ). The diagnostic criteria for CKD include a decreased eGFR [<60 ml/min/1.73 m 2 ) or an evidence of kidney damage such as albuminuria (albumin excretion rate ≥30 mg/24 h; urinary albumin– creatinine ratio (UACR) ≥30 mg/g], urine sediment abnormalities, electrolytes, and other abnormalities due to tubular disorders, abnormalities detected by histology, and structural abnormalities detected by the imaging or history of kidney transplantation ( 26 ).…”

“…It is well established that CKD is associated with bacterial dysbiosis in the gut ( 2 – 8 ). The existence of gut microbiome alterations such as a reduction in bacterial diversity has been related to CKD ( 3 , 4 , 6 , 7 ). Moreover, several potential pathogenic bacteria, such as Enterobacteriaceae, Escherichia-Shigella , Klebsiella , and Pseudomonas increased in CKD patients ( 3 , 6 , 7 ), while bacteria with probiotic features, including Akkermansia , Bifidobacterium , Blautia , Faecalibacterium , Prausnitzii , Lactobacillaceae, and Roseburia , depleted ( 3 – 5 , 7 ).…”

“…The interaction between the microbiome and immunity in health and disease might drive the pathogenesis of renal disorders ( 15 ). For example, our previous study demonstrated that the depletion of Actinobacteria and Bifidobacterium in CKD patients predicted the serum high level of free light chain lambda (FLC λ) ( 3 ).…”

Effect of 6-Methoxybenzoxazolinone on the Cecal Microbiota of Adult Male Brandt’s Vole

“…Reduced abundances in unidentified Melainabacteria, family of the unidentified Melainabacteria and Prevotellaceae , and the unidentified genus Melainabacteria suggest that those bacteria are susceptible to the administration of 6-MBOA, which verifies the antimicrobial properties of 6-MBOA ( Wang et al, 2001 ; Wang and Ng, 2002 ; Martyniuk et al, 2006 ). Chloroalkane and chloroalkene degradation, a pathway also involved in xenobiotic biodegradation and metabolism ( Liu F. et al, 2021 ), was consistently observed to be dose-dependently improved by 6-MBOA administration in cecal microbiota of Brandt’s voles.…”