Gut dysbiosis, low-grade inflammation, and renal impairment severity in elderly diabetic nephropathy

Abstract

BACKGROUND

The specific mechanism of diabetic nephropathy (DN) has not been fully elucidated, and more and more evidence shows that the development of DN is related to intestinal flora imbalance and micro-inflammatory state process, and this mechanism urgently needs to be further clarified by relevant research.

AIM

To investigate the correlation between intestinal microbiota dysbiosis, low-grade inflammatory status, renal function impairment, and disease severity in older patients with DN, in order to provide a basis for the prevention and therapeutic intervention of DN.

METHODS

We enrolled 167 older patients with DN, diagnosed in the Department of Nephrology between June 2020 and June 2023. Eighty-five patients with type 2 diabetes mellitus (without DN) were enrolled to serve as the control group. A one-year follow-up observation was conducted. We compared the differences in gut microbiota composition, levels of inflammatory markers, and renal function indicators between the two groups, and the characteristics of gut microbiota and the changing patterns of inflammatory markers across different stages of disease progression.

RESULTS

In the DN group, the Chao, Ace, and Shannon indices were significantly lower, while the Simpson index was significantly higher than the control group. The relative abundances of Bacteroides and Bifidobacterium were significantly lower, whereas the relative abundances of Clostridium, Butyricimonas, Klebsiella, Enterococcus, Veillonella, and Megamonas were significantly higher than those in the control group (P < 0.05). Estimated glomerular filtration rate was positively correlated with the Chao, Ace, and Shannon diversity indices of the gut microbiota, as well as with the relative abundances of Bacteroides, Bifidobacterium, and Akkermansia, and was negatively correlated with the relative abundances of Clostridium, Klebsiella, and Enterococcus (P < 0.05). Logistic regression analysis indicated that lower Chao, Ace, and Shannon indices and higher Simpson index were associated with an increased risk of developing DN. After one year of follow-up, patients in the progression group exhibited a significantly greater decrease in Chao, Ace, and Shannon indices and a greater increase in Simpson index than the stable group. The reduction in the relative abundances of Bacteroides, Clostridium, Bifidobacterium, and Butyricimonas, as well as the increase in Klebsiella, Enterococcus, Veillonella, and Megamonas, were significantly more pronounced in the progression group than in the stable group (P < 0.05). Regression analysis indicated that greater declines in Chao, Ace, and Shannon indices and Bacteroides relative abundance, along with greater increases in Simpson index and Enterococcus relative abundance, were associated with a more rapid decline in renal function.

CONCLUSION

The onset and progression of DN in older patients with diabetes are closely associated with gut microbiota composition. The more severe the dysbiosis, the lower the abundance of beneficial bacteria and the higher the abundance of harmful bacteria, leading to an increased risk of both DN occurrence and disease progression.

Keywords: Diabetic nephropathy; Intestinal flora imbalance; Microinflammatory state; Renal function damage; Glycometabolism; Lipid metabolism

Core Tip: At present, there are many studies on the relationship between intestinal microbiota and inflammation level and the development of diabetes, but the relationship between intestinal microbiota and the development of diabetic nephropathy (DN) is still unclear. This study investigated elderly patients with DN and revealed that they have dysbiosis of the gut microbiota and inflammatory response, which worsen with disease progression. We expect that these results will provide reference for the prevention and treatment of secondary DN in diabetic patients.