Fermented milk products can improve the immunity of the intestinal mucosa

Fermented milk products can improve the immunity of the intestinal mucosa

In a study recently published in the journal Immunological letters Researchers examined the role of fermented milk products and milk starters in modulating intestinal mucosal immunity.

The intestinal microbiota significantly influences the modulation of mucosal immunity and the role of the intestinal barrier. Accordingly, dysbiosis is associated with the breakdown of mucosal immunological homeostasis, leading to inflammatory bowel disease (IBD). In this context, probiotic bacteria can maintain internal homeostasis to promote health. Despite being our main source of live and active bacteria, including lactic acid bacteria (LAB) and propionibacteria (PAB), surprisingly little is known about the effects of fermented milk products on the human gut microbiota.

Review: Dairy starters and fermented milk products modulate the immunity of the intestinal mucosa. Photo credit: Peddalanka Ramesh Babu / Shutterstock

Milk starter as individual strains - in vivo effects of Streptococcus thermophilus

Most of the research on the S. thermophilus strain to date has been conducted in colitis-related settings. Compared to a placebo, research shows that taking S. thermophilus YIT2001 before colitis induction prevented colitis, reduced the disease activity index, and reduced the amount of lipid peroxide in the colonic mucosa.

Other S. thermophilus strains showed no protective effect, demonstrating the strain-dependent nature of the immunomodulatory effects. The study showed that the lower severity of colitis could be facilitated by the antioxidant activity of active strains of S. thermophilus. Furthermore, S. thermophilus ST28 ingestion significantly reduced the generation of interleukin (IL)-17 and the proportion of T helper (Th)-17 cells in the population of lamina propria lymphocytes in a dextran sulfate sodium (DSS)-induced colitis model. Therefore, this strain inhibits the Th17 response in intestinal inflammation. Consumption of S. thermophilus NCIMB 41856 delayed the onset of colitis, reduced the translocation of bacteria into the colon tissue, and minimized clinical symptoms such as gastrointestinal bleeding and body weight loss.

Another mouse colitis model used intrarectally administered trinitrobenzene sulfonic acid (TNBS) to evaluate S. thermophilus CRL803. Compared to mice with colitis without probiotic treatment, consumption of this strain has been shown to reduce histological and macroscopic damage scores, microbial translocation to the liver, inducible nitric oxide synthase-positive (iNOs+) cells in the colon, and pro-inflammatory cytokines.

Ingestion of S. thermophilus CRL 808 reduced the induced mucositis. This included a decrease in diarrhea score and repair of intestinal architecture, while no change in cytokine levels was observed. In contrast, a strain of S. thermophilus, CRL 415, did not show a comparable protective effect. Another investigation showed that consumption of S. thermophilus ST4 benefited mice suffering from fluorouracil (5FU) mucositis by reducing body weight loss, loss of appetite and diarrhea, while preserving the epithelial structure of the colon and small intestine and reducing intestinal inflammation.

In vivo effects of Lactobacillus delbrueckii

It has been shown that L.delbrueckii subsp. lactis CNRZ327 reduces gastrointestinal inflammation in vivo. Consumption reduced body weight loss, microscopic and macroscopic signs of DSS-induced colitis in the digestive tract of test mice, and increased survival. It also affects cytokine production, including IL-6 and transforming growth factor-β (TGF-β) in the spleen and IL-6, IL-12, and TGF-β in the colon. In the cecal lymph nodes, it also led to an increase in CD4+ FOXP3+ regulatory T cells. It has been shown that L.delbrueckii subsp. bulgaricus prevents cancer associated with colitis. In an azoxymethane/DSS mouse model, it reduced intestinal and tumor levels of cytokines such as IL-6, IL-17, IL-23, IL-1β and TNF-β, inhibited total tumor volume and average tumor size, and decreased clinical signs of intestinal inflammation.

In vitro mechanisms of Lactobacillus delbrueckii

Exopolysaccharides from L. delbrueckii may also contribute to the immunomodulatory effects of this organism. L. delbrueckii and its exopolysaccharide reduce the inflammatory response caused by enterotoxigenic Escherichia coli in porcine intestinal cells. An increase in resistance to rotavirus infection results from such treatment. L. delbrueckii exopolysaccharides influence the immunological response triggered by the activation of Toll-like receptor 3 (TLR3) in these porcine cells. They increased the expression of MxA, ribonuclease (RNase) L, interferon (IFN)-alpha and IFN-β after activation with the TLR agonist polyinosinic-polycytidylic acid (poly(I:C)).

In vivo effects of Lactobacillus helveticus

L. helveticus NS8 prevented mice from developing TNBS-induced colitis and demonstrated anti-inflammatory abilities. Specifically, it prevented TNBS-induced weight loss, lowered Wallace score, and reduced histological damage. The same strain was later shown to inhibit colitis-associated colorectal tumorigenesis by regulating inflammatory growth and microbial homeostasis. Consumption of L. helveticus NS8 reduced the amount and severity of tumor hyperplasia, suppressed nuclear factor κB (NF-κB) activation, increased the anti-inflammatory cytokine IL-10, and reduced the number of T cells producing IL-17.

In vitro mechanisms of Lactobacillus helveticus

L. helveticus NS8 promoted immunomodulatory IL-10 secretion when co-cultured with peripheral blood mononuclear cells (PBMCs). Furthermore, it reduced the lipopolysaccharide (LPS)-induced pro-inflammatory response in the mouse macrophage cell line RAW264.7. Furthermore, L. helveticus SBT2171 was shown in vitro to inhibit lymphocyte proliferation by modulating the c-Jun N-terminal kinase (JNK) signaling pathway. Furthermore, it increased A20 expression through TLR-2 signaling and reduced lipopolysaccharide-induced activation of mitogen-activated protein kinases and NF-κB in peritoneal macrophages.

Overall, the study results demonstrated the healing ability of LAB and PAB strains. Notably, only certain strains within each species actively promote intestinal homeostasis. To investigate the mechanisms underlying the complex, multifaceted interactions between bacteria and the host intestinal system, it is necessary to screen large numbers of strains.

Reference:

• Nassima Illikoud, Marine Mantel, Malvyne Rolli-Derkinderen, Valérie Gagnaire, Gwénaël Jan, Milchstarter und fermentierte Milchprodukte modulieren die Darmschleimhautimmunität, Immunology Letters, 2022, ISSN 0165-2478, DOI: https://doi.org/10.1016/j.imlet.2022.11.002, https://www.sciencedirect.com/science/article/pii/S016524782200150X

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