Combined oral intake of short and long fructans alters the gut microbiota in food allergy model mice and contributes to food allergy prevention

BMC Microbiology · 9 authors, 5 centres

AI SUMMARY

FIDELITY 100%

POPULATION5-week-old female BALB/c mice (n=28) with OVA-induced food allergy

INTERVENTIONOral administration of 5% 1-kestose (Kes), 5% inulin (Inu), or 2.5% Kes + 2.5% Inu in AIN-93G diet for 8 weeks

COMPARISONOVA-induced allergy group (OVA group) and non-allergic control group (Ctrl group) fed standard AIN-93G diet

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TL;DR

In an ovalbumin-induced food allergy mouse model, combined intake of short-chain fructan (1-kestose) and long-chain fructan (inulin) suppressed allergy symptoms more effectively than either alone. The combination significantly reduced allergy scores, rectal temperature drop, and OVA-specific IgE, while increasing total IgA and anti-inflammatory cytokine IL-10. These effects were linked to distinct changes in gut microbiota, including restoration of Parabacteroides and Alloprevotella species and increased short-chain fatty acid production, suggesting a microbiota-mediated allergy prevention mechanism.

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**Background:** Food allergies are a growing public health concern, affecting 3–6% of children in developed countries. Gut microbiota dysbiosis has been implicated in food allergy pathogenesis. Prebiotic fructans, such as short-chain 1-kestose (Kes, degree of polymerization [DP]=3) and long-chain inulin (Inu, DP up to 60), may modulate the microbiota and immune responses. This study hypothesized that combined intake of Kes and Inu would have stronger food allergy-preventive effects than either alone, due to different mechanisms.

**Methods:** Twenty-eight 5-week-old female BALB/c mice were divided into five groups: control (Ctrl, n=5), OVA-induced allergy (OVA, n=5), OVA + Kes (Kes, n=6), OVA + Inu (Inu, n=6), and OVA + Kes+Inu (Kes+Inu, n=6). Mice were fed experimental diets (AIN-93G-based) for 8 weeks, with 5% cellulose replaced by 5% Kes, 5% Inu, or 2.5% Kes+2.5% Inu. Allergy was induced by intraperitoneal OVA injections (100 µg OVA + alum at week 2, then 50 µg OVA + alum at weeks 4–8). At week 8, mice were orally challenged with 50 mg OVA. Allergic symptoms were scored (0–5), rectal temperature measured, and serum and fecal samples collected for ELISA (OVA-specific IgE, IgA, total IgA). Peyer's patches were analyzed for cytokine mRNA (IL-2, IL-4, IL-6, IL-10) by RT-qPCR. Fecal microbiota was profiled by 16S rRNA amplicon sequencing (V3-V4 region, Illumina MiSeq). GH32 gene copy numbers of Parabacteroides distasonis and P. goldsteinii were quantified by qPCR. Enzymatic activity of GH32 enzymes was tested using E. coli surface display. Cecal short-chain fatty acids (SCFAs: acetate, propionate, n-butyrate) and lactate were measured by HPLC.

**Key Results:** - **Allergy scores:** OVA group had significantly higher scores than Ctrl (P<0.0001). All fructan groups (Kes, Inu, Kes+Inu) had significantly lower scores vs. OVA (P<0.05 to P<0.0001). The Kes+Inu group showed the most pronounced suppression. - **Rectal temperature:** OVA group had a significant decrease (P<0.0001 vs. Ctrl). Kes and Kes+Inu groups significantly attenuated the drop (P<0.05 vs. OVA). - **Immunoglobulins:** OVA-specific IgE and IgA were significantly increased in OVA group (P<0.0001 vs. Ctrl) and significantly suppressed by all fructan treatments (P<0.05 to P<0.0001). Total IgA was significantly decreased in OVA group (P<0.05 vs. Ctrl) and significantly restored only in Kes+Inu group (P<0.05 vs. OVA). - **Cytokines:** IL-4 mRNA was significantly increased in OVA group (P<0.0001 vs. Ctrl) and significantly suppressed by all fructan groups (P<0.05 to P<0.0001). IL-10 mRNA was not different between OVA and Ctrl, but was significantly increased in Kes and Kes+Inu groups (P<0.05 vs. OVA). IL-2 and IL-6 showed no significant differences. - **Gut microbiota:** Alpha diversity (Shannon index) was significantly reduced in all fructan groups vs. OVA (P<0.05 to P<0.01). Beta diversity (weighted UniFrac) showed significant separation between Ctrl and OVA (P=0.006) and between OVA and each fructan group (Kes P=0.006, Inu P=0.003, Kes+Inu P=0.004). At phylum level, OVA group had significantly lower Bacteroidota and higher Firmicutes vs. Ctrl. Within Bacteroidota, genera Parabacteroides B 862,066 and Alloprevotella were significantly reduced in OVA group (P<0.05) and restored in fructan groups, especially Kes-fed groups (P<0.05 to P<0.001). P. distasonis abundance was significantly increased in Kes and Kes+Inu groups (P<0.05 vs. OVA); P. goldsteinii was significantly increased in Inu and Kes+Inu groups (P<0.05 vs. OVA). - **GH32 gene copy numbers:** GH32 copies of P. distasonis were significantly increased in Kes and Kes+Inu groups (P<0.05 vs. OVA); GH32 copies of P. goldsteinii were significantly increased in Inu and Kes+Inu groups (P<0.05 vs. OVA). Enzymatic assays confirmed that GH32 from P. distasonis degraded Kes, and GH32 from P. goldsteinii degraded Inu. - **SCFAs and lactate:** Acetate was significantly increased in Kes+Inu group (P<0.05 vs. OVA). Propionate was significantly increased in Kes group (P<0.05 vs. OVA). Lactate was significantly increased in Inu and Kes+Inu groups (P<0.05 vs. OVA). n-Butyrate showed no significant changes.

**Clinical Implications:** This study demonstrates that combined intake of short and long fructans (Kes+Inu) provides superior food allergy prevention compared to single fructans in a mouse model. The mechanisms involve distinct modulation of gut microbiota: Kes promotes P. distasonis and propionate production, while Inu promotes P. goldsteinii and lactate production, both leading to anti-inflammatory cytokine (IL-10) upregulation and Th2 cytokine (IL-4) suppression. These findings suggest that tailored prebiotic combinations could be a safe, dietary strategy for food allergy prevention. However, human studies are needed to confirm efficacy and safety in allergic populations.

PICO

PPOPULATION

5-week-old female BALB/c mice (n=28) with OVA-induced food allergy

IINTERVENTION

Oral administration of 5% 1-kestose (Kes), 5% inulin (Inu), or 2.5% Kes + 2.5% Inu in AIN-93G diet for 8 weeks

OOUTCOME

Allergenic symptom score, rectal temperature change, OVA-specific IgE and IgA, total IgA, cytokine gene expression (IL-4, IL-10), gut microbiota composition (16S rRNA sequencing), short-chain fatty acid concentrations (acetate, propionate, butyrate, lactate), and GH32 gene copy numbers

STUDY TYPE

RCT

SPECIALTY

nutrition

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FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10515425

Combined oral intake of short and long fructans alters the gut microbiota in food allergy model mice and contributes to food allergy prevention

BMC Microbiology

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ABSTRACT

Background It has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model. Results Oral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella , which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides , the relative abundances of Parabacteroides distasonis , Parabacteroides goldsteinii , and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups. Conclusion Combined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit. Supplementary Information The online version contains supplementary material available at 10.1186/s12866-023-03021-6.

CITATION EXPORT

Hideaki Takahashi, Tadashi Fujii, Saki Yamakawa et al.. Combined oral intake of short and long fructans alters the gut microbiota in food allergy model mice and contributes to food allergy prevention. BMC Microbiology. (2023). https://doi.org/10.1186/s12866-023-03021-6

AUTHORS

9 · 5 CENTRES

Hideaki Takahashi, Tadashi Fujii, Saki Yamakawa, Chikako Yamada, Kotoyo Fujiki, Nobuhiro Kondo, Kohei Funasaka, Yoshiki Hirooka, Takumi Tochio

1https://ror.org/01cpxhg33grid.444512.20000 0001 0251 7132Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Aichi Japan
2https://ror.org/046f6cx68grid.256115.40000 0004 1761 798XDepartment of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi Japan
3https://ror.org/046f6cx68grid.256115.40000 0004 1761 798XDepartment of Medical Research on Prebiotics and Probiotics, Fujita Health University, Toyoake, Aichi Japan
4Research and Development Division, Itochu Sugar Co., Ltd., Hekinan, Aichi Japan
5WELLNEO SUGAR Co., Ltd., Tokyo, Japan