Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases

Abstract

Objective: Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases.

Methods: We collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis.

Results: Regarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group (p < 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of Clostridiales, Clostridia, Firmicutes, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, Actinobacteria, Veillonellaceae, Longum, Copri, Megamonas and Callidus than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the Lachnospiraceae in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group.

Conclusion: The disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases.

Keywords: gastrointestinal diseases; gut; immunology; microbiota; serum.

Figure 1

Evaluate the immune function of the disease and the HC groups by measuring the levels of six serum cytokines.

Figure 2

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Figure 3

Analysis of microbial communities contributing significantly to intergroup differences. (A) Differences in species abundance between ID and HC groups. (B) Differences in species abundance between SD and HC groups.

Figure 4

Association of microbial communities with clinical characteristics. (A) Correlation matrix of species and clinical parameters in the ID group vs. HC group. Red indicates a positive correlation, while blue indicates a negative correlation. *, ** and *** represent p < 0.05, p < 0.01, and p < 0.001, respectively; the number of significant correlations for the 5 species with the most frequent correlations and 5 clinical characteristics with the most frequent correlations (only the top five are listed). (B) Correlation matrix of species and clinical parameters in the SD group vs. HC group. Red indicates a positive correlation, while blue indicates a negative correlation. *, ** and *** represent p < 0.05, p < 0.01, and p < 0.001, respectively; the number of significant correlations for the 5 species with the most frequent correlations and 5 clinical characteristics with the most frequent correlations (only the top five are listed).