1769: HIGH-FIBER DIET FAVORABLY INFLUENCES INNATE AND ADAPTIVE IMMUNE RESPONSE IN A MOUSE MODEL OF SEPSIS

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Introduction: Sepsis is a life-threatening syndrome characterized by dysregulated immune response to infection. Emerging evidence suggests that a high fiber diet may be protective through gut barrier integrity and immune modulation. This study investigates the effect of dietary fiber supplementation on immune function and gut-barrier integrity in sepsis, with implications for future nutritional interventions. Methods: Peritoneal sepsis was induced using cecal ligation and puncture (CLP) in mice following a two-week diet of high (HF) or low (LF) fiber. Stimulated ELISpot assay was used on splenocytes to quantify interferon (IFN)-γ and tumor necrosis factor (TNF) production in response to anti-CD3/CD28 or lipopolysaccharide (LPS). Flow cytometry was used to determine the distribution of CD4+ and CD8+ T-cells. To evaluate gut barrier integrity and systemic inflammation, frozen sections of intestine and liver were prepared and assessed for mucosal thickness and oxidative stress. Results: Mice from the high fiber group trended towards improved 96-hour survival but did not meet statistical significance (66.2% in HF, n=60; 51.7% in LF, n=60; p>0.5). LPS simulated TNF production trends higher in the HF group (62 spots (SFU) ± 81.6) compared to LF (32 SFU ± 24.2) (p=0.2543). Unstimulated IFN-γ, a marker of inflammation, was higher in low fiber (115 SFU ± 101.5) than high fiber (65 SFU ± 50.9) (p=0.04). There was no significant difference in simulated IFN-γ between the HF group (338 SFU ± 269.2) and LF group (403 SFU ± 319.4) (p=0.9). There was no difference between the two groups for CD4+ and CD8+ T-cells. Histological observation has yet to be completed, however will be included in the final analysis. Conclusions: The present study demonstrates encouraging immunologic changes in immune function and response to sepsis in CLP mice after only two weeks receiving a high fiber regimented diet. Spontaneous IFN-γ production decreased, indicating decreased inflammation, and increased TNF responsiveness to LPS stimulation could demonstrate improved monocyte function. Furthermore, while not statistically significant, high fiber trended towards protection from sepsis mortality. These data support future studies in the immunologic effects of high fiber dietary supplementation in sepsis.

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