Renal malignancy is a tumor type that poses a serious threat to human health, and its pathogenesis has not yet been fully elucidated45. In recent years, more and more studies have indicated that intestinal flora may play an important role in the pathogenesis of renal malignant tumors46. In the present study, the results of MR analysis revealed the intestinal flora that are causally associated with the pathogenesis of renal malignant tumors at the level of phylum, order, family, and genus, specifically the genera LachnospiraceaeUCG010, Akkermansia, and Haemophilus47. These results provide new insights into the relationship between intestinal flora and the development of renal malignancies.
Actinobacteria are a group of Gram-positive bacteria commonly found in the environment and in humans, and are widespread in environments such as soil, water bodies and plant surfaces. In the human body, Actinobacteria are found in the oral cavity, skin and intestinal tract. It was found that the relative abundance of Actinobacteria in the intestinal flora had a negative causal effect with the development of renal malignancies48. This implies that individuals with relatively less Actinobacteria are more likely to develop renal malignancies49. Although the specific mechanisms underlying the association between Actinobacteria and renal malignancy have not been fully elucidated, their interactions with other beneficial flora and effects on the host immune system may play a regulatory role in tumorigenesis50. Further studies are needed to delve into the mechanisms of this negative causal effect.
FamilyXI (also known as Bacteriophage XI) is a class of bacteria that is not yet widely understood, and its role and function in the intestinal flora are currently unknown51. However, studies have shown that FamilyXI may play a negative causal role in the pathogenesis of renal malignancies. Its relative abundance is negatively correlated with the development of renal malignancies, i.e., individuals with relatively more FamilyXI may be less likely to develop renal malignancies52. Although FamilyXI has been poorly studied, this finding may provide clues for further exploration of its relationship with renal malignancies and may help to reveal its potential functional and ecological roles in the intestinal flora53.
Veillonella is a group of Gram-negative anaerobic bacteria that are widely distributed in the oral, intestinal, and respiratory tracts of the human body. There is a negative causal effect between the relative abundance of Veillonella in the intestinal flora and the incidence of renal malignant tumors, i.e., individuals with higher relative abundance of Veillonella may be less likely to develop renal malignant tumors33. The study suggests that Veillonella may have an impact on tumorigenesis by regulating the intestinal microenvironment and affecting the intestinal mucosal barrier and immune system54. However, the exact mechanism still needs further research and validation.
On the contrary, Streptococcaceae are a family of Gram-positive cocci that are commonly found in the human body in the oral cavity, pharynx, and intestinal tract, etc55. There is a positive causal effect between the relative abundance of Streptococcaceae in the intestinal flora and the development of renal malignant tumors, i.e., individuals with a relatively higher abundance of Streptococcaceae are more prone to develop renal malignant tumors. This may be related to Streptococcaceae metabolites, immune regulation, and inflammatory responses. Overproliferation of Streptococcaceae may lead to an inflammatory state, which may affect tumor development and immune system homeostasis. However, the specific molecular mechanisms have not been fully elucidated and more in-depth studies are needed to explore the association between Streptococcaceae and renal malignancies56.
Intestinibacter, a genus of gut bacteria that is not yet widely understood, and its association with renal malignant tumors has also been the subject of recent research. There is a positive causal effect between the relative abundance of Intestinibacter in the intestinal flora and the development of renal malignant tumors, i.e., individuals with a relatively higher abundance of Intestinibacter are more likely to develop renal malignant tumors57. Intestinibacter may be associated with the development of renal malignancies through pathways such as metabolites, activation of immune responses, or influence on cell signaling pathways58. However, the genus Intestinibacter is less studied and further studies are needed to delve into its function in the intestinal flora and its specific relationship with renal malignancy.
On the other hand, the results of MR analysis in the present study also showed a negative causal association between Intestinibacter of the genus Haemophilus and the development of renal malignancies. Haemophilus, the genus Haemophilus, is a group of gram-negative, causticotrophic bacteria. Observational studies have shown that the relative abundance of this group of bacteria is lower in patients with renal malignancies compared to sedentary healthy individuals59. Although a negative causal association exists, further research is needed regarding the specific mechanism of this association. A possible explanation is that intestinal bacteria of the genus Haemophilus may play a protective role in the pathogenesis of renal malignancies, inhibiting tumor development by modulating immune responses or metabolic pathways.
Taken together, these findings suggest a complex interaction between intestinal flora and elevated renal malignant tumor development. The genera LachnospiraceaeUCG010 and Akkermansia may have a contributory role in renal malignant tumor development, whereas the genus Haemophilus may be negatively and causally associated with the development of renal malignant tumors60. However, in the study exploring the association between intestinal flora and the development of renal malignant tumors, we cannot ignore some potential drawbacks and limitations. First, the small amount of data in this study is a concern. Although causal associations between some flora at the level of order and family and renal malignant tumors were revealed by MR analysis, the small sample size may lead to insufficient statistical validity of the results, thus affecting the reliability and generalizability of the conclusions. Future studies should expand the sample size to cover as wide a population as possible in order to assess the relationship between flora and renal malignancy more comprehensively61. Secondly, the study may be subject to selective bias. The sample source and study design of this study may have led to greater emphasis on the detection and study of certain flora, thus neglecting other flora associated with renal malignancy62. This selective bias may have resulted in less than objective and comprehensive study results, compromising the overall understanding of the association between intestinal flora and renal malignancy63. To eliminate or mitigate the effect of bias, future studies should adopt a more comprehensive and systematic approach to assess the association between different flora and renal malignancy.
In summary, although this study revealed the association between some intestinal flora and the development of renal malignant tumors, it still suffers from the drawbacks of small data size, possible selective bias, limited study design, and complexity of flora. This needs to be overcome in the future by a larger sample size, a more rigorous study design, and a comprehensive analytical approach to better understand the relationship between intestinal flora and renal malignancies and to provide stronger support for the prevention and treatment of renal malignancies.