# Synergy between the prebiotic bovine milk oligosaccharides and the probiotic B. infantis improves gut barrier function in vivo

Mary Kristina Hamilton, Gaëlle Boudry, Maciej Chichlowski, Saumya Wickramasinghe, David A. Mills, Helen E Raybould

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Mary Kristina Hamilton, Gaëlle Boudry, Maciej Chichlowski, Saumya Wickramasinghe, David A. Mills, et al.. Synergy between the prebiotic bovine milk oligosaccharides and the probiotic B. infantis improves gut barrier function in vivo. Probiotics, prebiotics, and the host microbiome: the science of translation, Jun 2013, New York, United States. 2013, Probiotics, Prebiotics, and the Host Microbiome – Poster Abstracts. hal-01594925

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https://hal.science/hal-01594925

Submitted on 3 Jun 2020

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# Probiotics, Prebiotics, and
the Host Microbiome:
The Science of Translation

## Poster Session

Wednesday, June 12, 2013

6:00PM – 7:30PM
23.

ATTENUATION OF COLON INFLAMMATION BY PROBIOTIC LACTOBACILLUS REUTERI VIA HISTAMINE PRODUCTION

Chunxu Gao, BS<fnref n="1" />,<fnref n="2" />, Sanjiv Harpavat, MD, PhD<fnref n="1" />,<fnref n="2" />, Vanessa Jackson, BS<fnref n="1" />, Jennifer Spinler<fnref n="1" />,<fnref n="2" />,
Carissa Thomas PhD<fnref n="1" />, Peera Hemarajata, MD<fnref n="1" />,<fnref n="2" />, James Versalovic, MD, PhD<fnref n="1" />,<fnref n="2" />

Supplementation with certain probiotic *Lactobacillus reuteri* strains that naturally colonize the gut of mammals has been found effective at ameliorating intestinal inflammation in patients with IBD and in rodent colitis models, but the underlying mechanisms are unknown. Pangenomic studies revealed that among all sequenced *L. reuteri* strains, those with anti-inflammatory properties contain a complete *hdc* gene cluster which is responsible for synthesis and secretion of histamine, indicating a potential role for histamine in alleviation of inflammation. *L. reuteri* 6475 which contains an intact *hdc* gene cluster was found to suppress TNF production in activated THP-1 cells through the production of histamine and activation of histamine receptor 2 (H2R). Targeted mutagenesis of the *hdc* genes demonstrated diminished anti-TNF activity and loss of histamine production, indicating the anti-TNF activity of histamine in vitro. Using a trinitrobenzene sulfonic acid-induced mouse model of colitis, *L. reuteri* 6475 administration was found to protect eight-week female BALB/c mice against colitis, as indicated by significantly decreased weight loss, colonic damage graded by the Wallace score, and serum amyloid A protein concentrations compared to media control. The *hdcA* mutant of *L. reuteri* 6475 which failed to produce histamine showed diminished ability to attenuate colitis. Moreover, H2R was detected in the mouse colon by immunohistochemistry and blocking H2R with its specific antagonist ranitidine diminished the anti-inflammatory ability of *L. reuteri* 6475. These combined investigations indicate that *L. reuteri* 6475 attenuates experimental colitis via histamine production, which provides important insights into understanding the molecular mechanisms underlying probiotic immunomodulation.

24.

SYNERGY BETWEEN THE PREBIOTIC BOVINE MILK OLIGOSACCHARIDES AND THE PROBIOTIC B. INFANTIS IMPROVES GUT BARRIER FUNCTION IN VIVO

M Kristina Hamilton, BS<fnref n="1" />, Gaëlle Boudry, PhD<fnref n="2" />, Maciej Chichlowski, PhD<fnref n="1" />, Saumya Wickramasinghe, PhD<fnref n="1" />,
David A Mills, PhD<fnref n="1" />, Helen E Raybould, PhD<fnref n="1" />

Prebiotics and probiotics are used for treatment of GI disorders, such inflammatory bowel disease, irritable bowel syndrome, and recently, obesity; these disorders have altered gut microbiota, impaired intestinal barrier function, and inflammation. A synergistic relationship has been shown between prebiotic bovine milk oligosaccharides (BMO) and probiotic *Bifidobacterium longum subsp. infantis* (*B. infantis*) *in vitro* (Garrido et al, *Plos One*, 2011). The aim of the study was to assess the ability of BMO and *B. infantis* to restore intestinal permeability *in vivo*. Mice were fed a western diet (WD, 20% fat) or normal chow (NC, 10% fat) for seven weeks. For the final two weeks of the study, the diet of a subgroup of WD-fed mice was supplemented with BMO (7%). Weekly gavage of *B. infantis* was performed in all mice starting at week three. The presence of *B. infantis* was confirmed in the large intestine of all mice at the completion of the study. Intestinal tissue was mounted in Ussing chambers to evaluate intestinal permeability. Ingestion of WD compared to NC increased paracellular and transcellular flux in the large intestine; barrier function was restored by BMO supplementation. mRNA of the inflammatory marker TNFα was lower in intestine of BMO-supplemented compared to WD mice. Conditioned medium from *B. infantis*+BMO but not from *B. infantis*+lactose cultures protected against pro-inflammatory cytokine-induced alteration of barrier function in Caco-2 cells. The data support the hypothesis that *B. infantis*+BMO restores intestinal barrier function, thereby decreasing the passage of detrimental luminal contents causing inflammation.

<footnote n="1">¹Baylor College of Medicine, Houston, Texas</footnote>

<footnote n="2">²Texas Children's Hospital, Houston, Texas</footnote>

<footnote n="1">¹University of California Davis, Davis, California</footnote>

<footnote n="2">²INRA UR 1341 ADNC, St-Gilles, France</footnote>