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. 2025 Jul 29;14(15):2662.
doi: 10.3390/foods14152662.

Therapeutic Potential of Kelp Fucoidan in Rebiosis of Gut Microflora and Immune Homeostasis in Cyclophosphamide-Induced Immunosuppressed Mice

Yaqing Liu  1 , Ruining Kang  1 , Yanfei Zhao  1 , Heng Zhang  1 , Qingfeng Rong  2 , Shaoxuan Yu  1 , Yaoguang Chang  3 , Zhengpeng Wei  4 , Lanlan Zhu  1
Affiliations

Therapeutic Potential of Kelp Fucoidan in Rebiosis of Gut Microflora and Immune Homeostasis in Cyclophosphamide-Induced Immunosuppressed Mice

Yaqing Liu et al. Foods. .

Abstract

Recent studies indicate that fucoidan may play a crucial role in the metabolism and biological function of the intestinal flora. This study investigates the therapeutic potential of kelp fucoidan on the gut microbiota and immune homeostasis of cyclophosphamide-induced immunosuppressed mice. An immunosuppressive mouse model was established using cyclophosphamide, followed by administration of various kelp fucoidan doses (low-dose fucoidan: 50 mg/(kg·bw)/d, medium-dose fucoidan: 100 mg/(kg·bw)/d, and high-dose fucoidan: 150 mg/(kg·bw)/d) to the experimental groups. Changes in the gut microbiota structure were analyzed using 16S rRNA high-throughput sequencing, alongside simultaneous measurement of serum immune indicators and levels of short-chain fatty acids (SCFAs). Results indicate that kelp fucoidan significantly improved the thymus and spleen indices in immunosuppressed mice (p < 0.05) and elevated serum levels of IgM, IgG and IL-4. Post-kelp fucoidan intervention, there was significant alteration in microbiota ecosystem restructuring, such as proliferation in probiotics, including Lactobacillus and Bifidobacterium, while opportunistic pathogens, such as Enterococcus and Escherichia coli, decreased. Furthermore, the levels of acetic, propionic, and butyric acids in the colonic contents of the kelp fucoidan group significantly improved (p < 0.01). This research demonstrates that kelp fucoidan enhances immune function in immunosuppressed mice by modulating gut microbiota balance and promoting short-chain fatty acid production.

Keywords: immunosuppressed mice; intestinal flora; kelp fucoidan; short chain fatty acid.

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Conflict of interest statement

Author Zhengpeng Wei is employed by the company Rongcheng Taixiang Food Co., Ltd., Rongcheng, Shandong. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Structural characterization of kelp fucoidan. Note: (A) molecular weight of kelp fucoidan; (B) monosaccharide composition of kelp fucoidan; (C) FTIR of kelp fucoidan.
Figure 2
Figure 2
Changes in DAI index in mice. Note: * p < 0.05, ** p < 0.01: Compared with the CON group.
Figure 3
Figure 3
Immune indexes in serum of mice. (A) Level of IFN-γ, (B) level of TNF-α, (C) level of IL-6, (D) level of IL-1β, and (E) level of IL-4. Note: * p < 0.05, ** p < 0.01: compared with the CON group; # p < 0.05, ## p < 0.01: compared with the CTX group.
Figure 4
Figure 4
Serum IgG and IgM levels of mice. (A) Level of IgG, (B) level of IgM. Note ** p < 0.01: compared with the CON group; ## p < 0.01: compared with the CTX group.
Figure 5
Figure 5
Dilutive curve based on OTU levels of mice intestinal flora. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 6
Figure 6
Shannon index based on OTU levels of mice intestinal flora. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 7
Figure 7
Difference analysis of alpha diversity index in intestinal flora of mice. (A) Chao1 index, (B) ACE index, (C) Shannon index, and (D) Simpson index. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 8
Figure 8
PCoA analysis and OTU quantity distribution of intestinal flora. (A) PCoA analysis, (B) OTU quantity distribution. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 9
Figure 9
Difference analysis of flora abundance in each treatment group. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 10
Figure 10
Differences analysis of intestinal flora in different phyla of each treatment group. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 11
Figure 11
Abundance analysis of bacteria from different families. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 12
Figure 12
Cluster analysis of horizontal intestinal flora. In feces: FBKB: CON group, FBMX: CTX group, YZT: FH group, YZTZ: FM group, YZTD: FL group; among colonic contents: ZZKB: CON group, ZZMX: CTX group, ZZYZT: FH group, ZZYZTM: FM group, ZZYZTD: FL group.
Figure 13
Figure 13
Analysis of SCFAs in colon contents of mice. (A) Content of acetic acid, (B) content of propionic acid, (C) content of butyric acid, (D) content of isobutyric acid, (E) content of valeric acid, and (F) content of isovaleric acid. Note: * p < 0.05, ** p < 0.01: compared with the CON group; # p < 0.05, ## p < 0.01: compared with the CTX group.
Figure 14
Figure 14
Analysis of SCFAs in feces of mice. (A) Content of acetic acid, (B) content of propionic acid, (C) content of butyric acid, (D) content of isobutyric acid, (E) content of valeric acid, and (F) content of isovaleric acid. Note: * p < 0.05, ** p < 0.01: compared with the CON group ## p < 0.01: compared with the CTX group.
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