Oral Treatment with the Pectin Fibre Obtained from Yellow Passion Fruit Peels Worsens Sepsis Outcome in Mice by Affecting the Intestinal Barrier

Abstract

The biological activities of plant-derived soluble dietary fibres (SDFs) have been widely investigated. Pectin from yellow passion fruit (YPF-peSDF) peels was suggested as a protective macromolecule in ulcers and colitis due to its antioxidant and anti-inflammatory properties. Sepsis has high mortality and morbidity and is characterised by inflammatory and oxidative stress imbalances. Evidence suggests that pectins may aid sepsis treatment; however, the effects of YPF-peSDF on sepsis remain unclear. Herein, polymicrobial sepsis was induced by cecal-ligation and puncture in mice treated with YPF-peSDF (1 and 10 mg/kg; gavage). YPF-peSDF accelerated mortality, reaching 100% in 24 h. Inflammation was present in the colons and small intestines (SI) of both vehicle- and fibre-treated mice. Although crypt depth and width, and villus height were preserved in the SI of septic mice administered YPF-peSDF, they exhibited exacerbated muscle layer atrophy and mucosa and submucosa hypertrophy, along with shortened enterocytes. Larger crypts and shorter enterocytes were noted in their colons in comparison with vehicle-controls. YPF-peSDF also reduced inflammatory cell numbers and exacerbated IL-6 levels in peritoneal lavage fluid (PELF) samples. YPF-peSDF modulated SI but not colon cytokines. Lipoperoxidation and antioxidant capacity levels were attenuated in PELF samples. Overall, in contrast to previous evidence, YPF-peSDF worsened polymicrobial sepsis outcomes in mice.

Keywords: pectin; sepsis; soluble dietary fibres.

Figure 1

YPF-peSDF effects on mortality and body temperature. (a) Percent survival over 96 h in animals (n = 14; 7 males and 7 females/group) treated with either YPF-peSDF (1 and 10 mg/kg) or vehicle (saline; 5 mL/kg) by gavage 1 h prior to sepsis induction by cecal-ligation and puncture (CLP). (b) Body temperature measurements were taken at baseline conditions (grey bars) and 18–24 h (premortality endpoint; white bars) following surgery from Sham and CLP mice (n = 12; 6 males and 6 females/group) treated with YPF-peSDF (1 and 10 mg/kg) or vehicle (saline; 5 mL/kg) by gavage 1 h prior to surgery. * p < 0.05, differs from baseline; ^# p < 0.05, differs from vehicle-treated CLP mice.

Figure 2

YPF-peSDF effects on small intestine histology. Histological analysis of small intestine samples obtained from Sham and cecal-ligation and puncture (CLP) mice (n = 6; 3 males and 3 females/group) treated with YPF-peSDF (10 mg/kg) or vehicle (saline; 5 mL/kg) 1 h prior to surgery. Small intestine (a) histopathological score, (b) total wall, (c) muscle layer, (d) submucosa and (e) mucosa thickness, crypt (f) depth and (g) width, villus (h) height and (i) width, enterocyte (j) height, and (k) width. Representative panels of the histological analysis, and (l) representative panels of histological analysis (20 and 40× magnification). Arrows indicate structural tissue loss, and brackets indicate specific intestinal structures. * p < 0.05; differs from vehicle-treated Sham animals. ^# p < 0.05; differs from vehicle-treated CLP mice.

Figure 3

YPF-peSDF effects on colonic histology. Histological analysis of colon samples obtained from Sham and cecal-ligation and puncture (CLP) mice (n = 6; 3 males and 3 females/group) treated with YPF-peSDF (10 mg/kg) or vehicle (saline; 5 mL/kg) 1 h prior to surgery. Colonic (a) histopathological score, (b) total wall, (c) muscle layer, (d) submucosa and (e) mucosa thickness, crypt (f) depth and (g) width, enterocyte (h) height and (i) width, and (j) representative panels of histological analysis (20 and 40× magnification). Arrows indicate structural tissue loss, and brackets indicate specific intestinal structures. * p < 0.05; differs from vehicle-treated Sham animals. ^# p < 0.05; differs from vehicle-treated CLP mice.

Figure 4

YPF-peSDF effects on cytokine generation. Peritoneal lavage fluid (PELF), small intestine, and colon samples were collected at the premortality endpoint (18–24 h) from Sham (n = 10; 5 males and 5 females/group) and cecal-ligation and puncture (CLP) mice (n = 12; 6 males and 6 females/group) treated with YPF-peSDF (10 mg/kg) or vehicle (saline; 5 mL/kg) 1 h prior to surgery. Levels of PELF (a) TNFα, (b) IL-6, and (c) IL-10; small intestine (d) TNFα, (e) IL-6, and (f) IL-10; and colon (g) TNFα, (h) IL-6, and (i) IL-10. * p < 0.05; differs from vehicle-treated Sham animals. ^# p < 0.05; differs from vehicle-treated CLP mice.

Figure 5

YPF-peSDF effects on oxidative stress. Peritoneal lavage fluid (PELF), small intestine, and colon samples were collected at the premortality endpoint (18–24 h) from Sham (n = 10; 5 males and 5 females/group) and cecal-ligation and puncture (CLP) mice (n = 12; 6 males and 6 females/group) treated with YPF-peSDF (10 mg/kg) or vehicle (saline; 5 mL/kg) 1 h prior to surgery. Levels of PELF (a) LPO, (b) TAC, and (c) GSH; small intestine (d) LPO, and (e) GSH, and colon (f) LPO and (g) GSH. * p < 0.05; differs from vehicle-treated Sham animals. ^# p < 0.05; differs from vehicle-treated CLP mice.