Dietary fiber guar gum-induced shift in gut microbiota metabolism and intestinal immune activity enhances susceptibility to colonic inflammation

ABSTRACT

With an increasing interest in dietary fibers (DFs) to promote intestinal health and the growth of beneficial gut bacteria, there is a continued rise in the incorporation of refined DFs in processed foods. It is still unclear how refined fibers, such as guar gum, affect the gut microbiota activity and pathogenesis of inflammatory bowel disease (IBD). Our study elucidated the effect and underlying mechanisms of guar gum, a fermentable DF (FDF) commonly present in a wide range of processed foods, on colitis development. We report that guar gum containing diet (GuD) increased the susceptibility to colonic inflammation. Specifically, GuD-fed group exhibited severe colitis upon dextran sulfate sodium (DSS) administration, as evidenced by reduced body weight, diarrhea, rectal bleeding, and shortening of colon length compared to cellulose-fed control mice. Elevated levels of pro-inflammatory markers in both serum [serum amyloid A (SAA), lipocalin 2 (Lcn2)] and colon (Lcn2) and extensive disruption of colonic architecture further affirmed that GuD-fed group exhibited more severe colitis than control group upon DSS intervention. Amelioration of colitis in GuD-fed group pre-treated with antibiotics suggest a vital role of intestinal microbiota in GuD-mediated exacerbation of intestinal inflammation. Gut microbiota composition and metabolite analysis in fecal and cecal contents, respectively, revealed that guar gum primarily enriches Actinobacteriota, specifically Bifidobacterium. Guar gum also altered multiple genera belonging to phyla Bacteroidota and Firmicutes. Such shift in gut microbiota composition favored luminal accumulation of intermediary metabolites succinate and lactate in the GuD-fed mice. Colonic IL-18 and tight junction markers were also decreased in the GuD-fed group. Importantly, GuD-fed mice pre-treated with recombinant IL-18 displayed attenuated colitis. Collectively, unfavorable changes in gut microbiota activity leading to luminal accumulation of lactate and succinate, reduced colonic IL-18, and compromised gut barrier function following guar gum feeding contributed to increased colitis susceptibility.

SUMMARY

• Guar gum increased susceptibility to colitis

• Guar gum-induced exacerbation of colitis is gut microbiota dependent

• Guar gum-induced shift in microbiota composition favored the accumulation of luminal intermediate metabolites succinate and lactate

• Guar gum-fed mice exhibited reduced colonic level of IL-18 and tight junction molecules.

• Exogenous IL-18 administration partly rescued mice from guar gum-induced colitis susceptibility

KEYWORDS:

• Added fiber
• dysbiosis
• inflammatory bowel disease
• succinate
• lactate
• Bifidobacterium
• interleukin-18 (IL-18)

Acknowledgments

The authors thank the Genom’IC platform (Institut Cochin, Paris, France) for its help in Illumina sequencing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The microbiota sequencing data that support the findings of this study will be openly available in the European Nucleotide Archive under accession number PRJEB64411.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2341457

Additional information

Funding

This work was supported by Career Development Award [ID# 597229] from Crohn’s and Colitis Foundation and NIH award [R01DK133334-01A1]. D.P. was supported by NIH grant [T32DK120509]. BC’s laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. [ERC-2018-StG- 804135], a Chaire d’Excellence from IdEx Université de Paris - ANR-18-IDEX-0001, an Innovator Award from the Kenneth Rainin Foundation, an award from the Fondation de l’Avenir [AP-RM-21-032], ANR grants EMULBIONT [ANR-21-CE15-0042-01] and DREAM [ANR-20-PAMR-0002] and the national program “Microbiote” from INSERM.