Evaluation of vitamin-producing and immunomodulatory lactic acid bacteria as a potential co-adjuvant for cancer therapy in a mouse model.

AIMS: To evaluate a mixture of selected lactic acid bacteria (LAB) (a riboflavin-producer, a folate-producer and an immunomodulatory strain) as co-adjuvant for 5-fluorouracil (5-FU) chemotherapy in cell culture and using a 4T1 cell animal model of breast cancer. METHODS AND RESULTS: The viability of Caco-2 cells exposed to 5-FU and/or LAB was analysed. Mice bearing breast tumour were treated with 5-FU and/or LAB. Tumour growth was measured. Intestinal mucositis (IM) was evaluated in small intestine; haematological parameters and plasma cytokines were determined. The bacterial mixture did not negatively affect the cytotoxic activity of 5-FU on Caco-2 cells. The LAB mixture attenuated the IM and prevented blood cell decreases associated with 5-FU treatment. Mice that received 5-FU and LAB mixture decreased tumour growth and showed modulation of systemic cytokines modified by both tumour growth and 5-FU treatment. The LAB mixture by itself delayed tumour growth. CONCLUSIONS: The mixture of selected LAB was able to reduce the side-effects associated with chemotherapy without affecting its primary anti-tumour activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This bacterial mixture could prevent the interruption of conventional oncologic therapies by reducing undesirable side-effects. In addition, this blend would provide essential nutrients (vitamins) to oncology patients.

Recent update on lactic acid bacteria producing riboflavin and folates: application for food fortification and treatment of intestinal inflammation.

Lactic acid bacteria (LAB), widely used as starter cultures for the fermentation of a large variety of food, can improve the safety, shelf life, nutritional value and overall quality of the fermented products. In this regard, the selection of strains delivering health-promoting compounds is now the main objective of many researchers. Although most LAB are auxotrophic for several vitamins, it is known that certain strains have the capability to synthesize B-group vitamins. This is an important property since humans cannot synthesize most vitamins, and these could be obtained by consuming LAB fermented foods. This review discusses the use of LAB as an alternative to fortification by the chemical synthesis to increase riboflavin and folate concentrations in food. Moreover, it provides an overview of the recent applications of vitamin-producing LAB with anti-inflammatory/antioxidant activities against gastrointestinal tract inflammation. This review shows the potential uses of riboflavin and folates producing LAB for the biofortification of food, as therapeutics against intestinal pathologies and to complement anti-inflammatory/anti-neoplastic treatments.

Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime.

Maternal immune activation (MIA) and poor maternal nutritional habits are risk factors for the occurrence of neurodevelopmental disorders (NDD). Human studies show the deleterious impact of prenatal inflammation and low n-3 polyunsaturated fatty acid (PUFA) intake on neurodevelopment with long-lasting consequences on behavior. However, the mechanisms linking maternal nutritional status to MIA are still unclear, despite their relevance to the etiology of NDD. We demonstrate here that low maternal n-3 PUFA intake worsens MIA-induced early gut dysfunction, including modification of gut microbiota composition and higher local inflammatory reactivity. These deficits correlate with alterations of microglia-neuron crosstalk pathways and have long-lasting effects, both at transcriptional and behavioral levels. This work highlights the perinatal period as a critical time window, especially regarding the role of the gut-brain axis in neurodevelopment, elucidating the link between MIA, poor nutritional habits, and NDD.

Soyamilk fermented with riboflavin-producing Lactobacillus plantarum CRL 2130 reverts and prevents ariboflavinosis in murine models.

It has been previously shown that Lactobacillus plantarum CRL 2130 is able to produce riboflavin in soyamilk. The aim of the present study was to evaluate the efficiency of this riboflavin-bio-enriched soyamilk to revert and/or prevent the nutritional deficiency of riboflavin using different animal models. When used to supplement the diets of previously depleted animals, it was shown that the growth, riboflavin status and morphology of the small intestines reverted to normal parameters and were similar to animals supplemented with commercial riboflavin. In the prevention model, the same tendency was observed, where animals that received soyamilk fermented with L. plantarum CRL 2130 did not show signs of riboflavin deficiency. This new bio-fortified soya-based product could be used as part of normal diets to provide a more natural alternative to mandatory fortification with riboflavin for the prevention of its deficiency.

Study of immune cells involved in the antitumor effect of kefir in a murine breast cancer model.

Administration of kefir and a kefir cell-free fraction (KF) to mice injected with breast tumor cells produced, locally in the mammary gland, different profiles of cells secreting cytokines. Here, the immune cell populations in mammary glands affected by the cyclic consumption of kefir or KF for 2 or 7 d were evaluated using a breast tumor model. Apoptosis was also assayed as another mechanism involved in tumor growth delay. The rate development of tumor cells, IgA(+) cells, and CD4+ and CD8+ T lymphocytes was monitored in mammary gland tissues. The number of Bcl-2(+) cells in the mammary gland was compared with the apoptosis observed in the tumor. Two-day cyclical administration of both products delayed tumor growth and increased the number of IgA(+) cells in the mammary gland. Changes in the balance between CD4+ and CD8+ cells in the mammary gland were observed in mice from the group fed KF cyclically for 2 d, such that the number of CD4+ cells increased when the number of CD8+ cells remained constant. Mice that received 2-d cyclic administration of KF showed significant increases in the number of apoptotic cells and decreases in Bcl-2(+) cells in the mammary gland, compared with the tumor control group. The present study allows a better understanding of the mechanisms (immune and nonimmune) involved in the antitumor effect observed in mice administered kefir or KF. The importance of nonmicrobial components released during milk fermentation to obtain the beneficial antitumor effects is also reported.

Study of cytokines involved in the prevention of a murine experimental breast cancer by kefir.

Previous studies have shown that compounds released during milk fermentation by Lactobacillus helveticus are implicated in the antitumour effect of this product. Here the effects of the consumption, during 2 or 7 days, of kefir or kefir cell-free fraction (KF) on the systemic and local immune responses in mammary glands and tumours using a murine hormone-dependent breast cancer model were studied. In the tumour control group, mice did not receive these products. At the end of the feeding period, mice were injected subcutaneously with tumour cells in the mammary gland. Four days post-injection, they received kefir or KF on a cyclical basis. Rate of tumour development, cytokines in serum; mammary gland tissue, and tumour isolated cells were monitored. Two-day cyclical administration of both products delayed tumour growth. Both kefir and KF increased IL-10 in serum and decreased IL-6(+) cells (cytokine involved in oestrogen synthesis) in mammary glands. Two-day cyclical administration of KF increased IL-10(+) cells in mammary glands and in tumours and decreased IL-6(+) cells in tumour. This study demonstrated the modulatory capacity of KF on the immune response in mammary glands and tumours and the importance of the administration period to obtain this effect.