Production of fructooligosaccharides byBacillus subtilisnatto CCT7712 and their antiproliferative potential

Abstract

Aims: Fructooligosaccharides (FOSs) known for their health properties and b-(2?6)-levan-type FOSs have shown prebiotic and immunomodulatory activities that overcome those of commercial b-(2?1)-FOSs, but costs do not favour their use. Moreover, FOSs can reach the bloodstream through the diet, and little is known about their direct effect on cells. The aim of this work was to produce high-content FOSs by Bacillus subtilis natto CCT7712 in a bioreactor using commercial sucrose and to evaluate their antiproliferative effects in OVCAR-3 cells. Methods and Results: FOS production reached 173Á60 g l À1 , 0Á2 vvm aeration and uncontrolled pH. Levan-type FOSs, composed of b-(2 ? 6) links and mainly GF 3 (6-nystose), were identified using RMN spectroscopy, FT-IR and ESI-MS. FOSs decreased the viability and proliferation of OVCAR-3 cells, and the effects were associated with an increased pro-inflammatory response by the induction of IL-8 and TNF-a, and the repression of ER-b genes. The metabolic profiles showed disruption of cellular homeostasis that can be associated with a decrease in proliferation. Conclusions: The high production of levan-type FOSs from B. subtilis natto CCT7712 in a bioreactor was achieved, and they showed antiproliferative potential in OVCAR-3 cells. Significance and Impact of the Study: FOS could be a good target for future therapeutic studies and commercial use.

Exopolysaccharide β-(2,6)-levan-type fructans have a molecular-weight-dependent modulatory effect on Toll-like receptor signalling

“…β-(2,1)-fructans are extensively investigated for their effect on the immune response and have been shown to interact with TLRs to elicit their response. 21 Although β-(2,6)-fructans presented similar effects on the immune response in human in vitro studies, 22,24,25 the mechanisms underlying the immunomodulatory function of β-(2,6)-…”

“…β-(2,1)-fructans are extensively investigated for their effect on the immune response and have been shown to interact with TLRs to elicit their response. 21 Although β-(2,6)-fructans presented similar effects on the immune response in human in vitro studies, 22,24,25 the mechanisms underlying the immunomodulatory function of β-(2,6)-fructans are not well understood. Since it was shown that β-(2,1)-fructans elicit their immunomodulatory response through TLR interaction, 7,29 we hypothesized that similar mechanisms might be involved in the immunomodulatory effects of β-(2,6)-fructans.…”

“…21 For example, microbial β-(2,6)fructans isolated from B. subtilis were shown to enhance the production of proinflammatory TNF-α and the chemokine IL-8 in human-derived ovarian carcinoma cells. 22 Microbial β-(2,6)fructans isolated from L. reuteri were shown to increase FOXP3+ CD4+ regulatory T-cells in rats, 23 and microbial β-(2,6)-fructan isolated from H. hepaticus increased the IL-10/ IL-6 ratio in vitro in bone marrow-derived macrophages. 24 Although much research has been performed on the possible immunological effects of fructans, the mechanisms underlying their immunomodulatory properties are, especially for β-(2,6)-fructans, less well understood.…”

Fructooligosaccharides (FOS) Production by Microorganisms with Fructosyltransferase Activity

“…Nevertheless, this could be reduced by using enzymes and specific microorganisms. In this context, some parameters of the bioprocesses are determinants for FOS production [63], for example, temperature, pH, agitation speed, oxygen flow, and the culturing medium composition [56,63]. The worldwide increase in the demand for FOS requires new substrates and processes to reduce costs, as well as addressing the global problem of excessive generation of agro-industrial waste on the planet [17].…”