Body mass index and fat influences the role of Bifidobacterium genus in lupus patients concerning fibrinogen levels

Abstract

Introduction: Metabolic disorders and autoimmune diseases elicit distinct yet interconnected manifestations of inflammation, which may be boosted by an excess of body adiposity. The purpose of this investigation was to analyze anthropometric, biochemical, and inflammatory/coagulation variables concerning patients diagnosed with systemic lupus erythematosus (SLE) exploiting low-grade metabolic inflammation (MI), as reference.

Methods: A population stratification by body mass index (BMI), allowed to assess the impact of adiposity on the putative role of gut microbiota composition on coagulation markers. A total of 127 participants with MI and SLE were categorized into two main groups based on their BMI, following WHO criteria: a low BMI group (<30 kg/m²) and a high BMI group (≥30 kg/m²). Each group included recorded data on demographics, comorbidities, and key clinical markers. Anthropometric and body composition variables, clinical features, and inflammatory/coagulation markers were measured while fecal 16S rRNA sequencing was examined at the genus Bifidobacterium. Regression models were fitted to evaluate the relationship between gut microbiota, inflammatory/coagulation markers, and body weight in these types of diseases.

Results: The study revealed worse clinical outcomes in anthropometric, body composition, and clinical markers in low-grade MI conditions as compared to SLE. However, inflammatory and coagulation markers such as C-reactive protein (CRP) and fibrinogen were significantly more elevated in patients with SLE, which was exacerbated by high BMI/ body fat as compared to the other screened groups. An interaction analysis revealed that fibrinogen levels showed different trends when Bifidobacterium was increased depending on BMI/adiposity, which evidenced an effect modification by this microorganism in patients with SLE.

Discussion: These findings underline that gut microbiota composition, particularly the presence of Bifidobacterium, may play a crucial role in modulating inflammation and coagulation processes in patients with SLE and high fat. These insights highlight the potential of targeting gut microbiota as a therapeutic strategy to mitigate inflammation and improve clinical outcomes in SLE patients.

Keywords: Bifidobacterium; body mass index; fibrinogen; low-grade metabolic inflammation; systemic lupus erythematosus.

Figure 1

The alpha diversity index (A,B) and principal coordinate analysis (C,D) show the comparison of microbial diversity in patients with low-grade MI and SLE according to BMI levels. Patients with low BMI are represented in orange, and those with high BMI are in blue. In panels (A,B) the differences in box heights and outliers allow comparing the internal diversity of each group (alpha diversity) according to BMI. These findings were verified using a t-test. In panels (C,D), the dispersion and spacing between the circles reflect the diversity between groups (beta diversity), where a larger distance implies more pronounced differences in microbial composition between patients with different BMI.

Figure 2

Cladogram and linear discriminant analysis between low-grade MI and SLE participants. Only taxa meeting a p < 0.05 and LDA score significant threshold | > 2| are shown. Red bacterial taxa statistically overrepresented in low-grade MI participants; green bacterial taxa overrepresented in participants with SLE (A). A bar plot shows the differential abundance of the Bifidobacterium genus, with red boxes for patients with low-grade MI and blue boxes for SLE (B). The ROC analysis demonstrates the model’s ability to differentiate between low-grade MI and SLE with an Area Under the Curve (AUC) of 77.36% and a 95% Confidence Interval of 69.32–85.4%, highlighting the importance of each feature in classification (C). In panel (A), the cladogram and linear discriminant analysis show the bacterial taxa with significant differences. This allows a quick comparison of which bacteria are most common in each disease. Panel (B) highlights the abundance of the genus Bifidobacterium, showing that the red and blue colors in the boxes correspond to patients with low-grade MI and SLE, respectively. Panel (C) presents an ROC curve assessing the classification performance of the model, with an AUC of 77.36%, indicating moderate accuracy in distinguishing between low-grade MI and SLE based on bacterial composition.

Figure 3

Predicted values of fibrinogen in SLE participants according to the relative abundance of Bifidobacterium and BMI status (A) and body fat levels (B) using linear regression models adjusted for age and sex. The red line represents participants with high BMI and the blue line represents participants with low BMI. The divergence between the lines suggests how the relative abundance of Bifidobacterium may differentially impact fibrinogen levels depending on BMI and body fat, highlighting the potential role of these factors in inflammation among SLE patients.