Abstract
BackgroundThe chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans.ResultsGut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 × 10−2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The α-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families.After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor’s body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 × 10−7), Rikenellaceae (r = 0.702, p = 3.9 × 10−4), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = − 0.445, p = 0.038) and Prevotellaceae RA (r = − 0.479, p = 0.024) and were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice’ weight gain and positively with gut bacterial ClpB-like gene function.ConclusionsIn summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma metabolomics profile in humans that could be partially transplanted to mice.9EgaQCzZBK_kpa4vXvXSr4Video
Highlights
The chaperone caseinolytic peptidase B protein homolog (ClpB), a bacterial protein, is a conformational antigen-mimetic of α-melanocytestimulating hormone (α-MSH) implicated in body weight regulation in mice
Gut bacterial ClpB-like gene function is associated with decreased body weight in humans A consecutive series of 131 subjects, 76 of them with obesity and their respective paired by sex and age controls, was studied (Table 1)
After adjusting for total energy intake and body weight, gut bacterial ClpB-like function was directly associated with proteins (r = 0.200, p = 0.032), carbohydrates (r = 0.224, p = 0.015), lipids (r = 0.303, p = 0.001), and fiber intake (r = 0.193, p = 0.037)
Summary
The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocytestimulating hormone (α-MSH) implicated in body weight regulation in mice. It has been observed that bacterial proteins which directly act in the brain via vagal stimulation or indirectly through immuneneuroendocrine mechanisms have an important role in this process [7, 9]. One of these bacterial proteins, the caseinolytic peptidase B protein homolog (ClpB), has been identified as a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) [10]. The α-MSH is an amino-acid derived from POMC that activates the melanocortin-4 receptor (MC4R) expressed in the hypothalamic paraventricular nucleus promoting the anorexigenic pathway and regulating satiety, energy, blood pressure, and growth [11]
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