Sialyllactose Sodium Salt Research Articles

Safety of 3'-sialyllactose (3'-SL) sodium salt produced by a derivative strain (Escherichia coliNEO3) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3'-sialyllactose (3'-SL) sodium salt as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3'-SL (sodium salt), but it also contains sialic acid, d-glucose, d-lactose, 3'-sialyllactulose and 6'-sialyllactose sodium salts and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli NEO3) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The applicant applies for the same uses and use levels as already assessed for 3'-SL sodium salt produced by a genetically modified strain of E. coli K-12 DH1, with the exception for the use in FS, which is proposed to be higher (from 0.5 to 1.0 g/day) in individuals from 3 years of age. Since the NF as a food ingredient would be consumed at the same extent as the already assessed 3'-SL sodium salt, no new estimates of theintakes have been carried out. The Panel notes that the maximum daily intake of 3'-SL from the proposed use of the NF in FS for individuals from 3 years of age (1.0 g/day) is lower than the estimated highest mean daily intake of 3'-SL in breastfed infants. FS are not intended to be used if other sources of 3'-SL are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.

Functional in vitro screening of probiotic strains for inoculation of piglets as a prophylactic measure towards Enterotoxigenic Escherichia coli infection

Enterotoxigenic Escherichia coli (ETEC), being the major cause of post-weaning diarrhoea (PWD) in newly weaned piglets, induces poor performance and economic losses in pig production. This functional in vitro screening study investigated probiotic strains for use in suckling piglets as a prophylactic strategy towards PWD. Nine strains were evaluated based on their ability to: enhance intestinal epithelial barrier function, reduce adherence of ETEC F18 to intestinal cells, inhibit growth of ETEC F18, and grow on porcine milk oligosaccharides. Strains included in the screening were of the species Lactobacillus, Enterococcus, Bifidobacterium and Bacillus. Our in vitro screening demonstrated genus-, species and strain-specific differences in the mode of action of the tested probiotic strains. Some of the tested bifidobacteria were able to grow on the two porcine milk oligosaccharides, 3′-sialyllactose sodium salt (3’SL) and Lacto-N-neotetraose (LNnT), whereas most lactic acid bacteria strains and both Bacillus subtilis strains failed to do so. All probiotic strains inhibited growth of ETEC F18 on agar plates. All but the bifidobacteria reduced binding of ETEC F18 to Caco-2 cell monolayers, with the Enterococcus faecium strain having the most profound effect. All three lactic acid bacteria and Bifidobacterium animalis subsp. lactis counteracted the ETEC F18-induced permeability across Caco-2 cell monolayers with the E. faecium strain exhibiting the most pronounced protective effect. The findings from this in vitro screening study indicate that, when selecting probiotic strains for suckling piglets as a prophylactic strategy towards PWD, it would be advantageous to choose a multi-species product including strains with different modes of action in order to increase the likelihood of achieving beneficial effects in vivo.

Evaluation of 6'-Sialyllactose Sodium Salt Supplementation to Formula on Growth and Clinical Parameters in Neonatal Piglets.

Oligosaccharides are complex, non-digestible glycans found in large abundance in human milk. The abundance and the profile of bovine milk oligosaccharides and bovine milk based in infant formula differ from those in human milk. Recently, some human milk oligosaccharides (HMOs) have been supplemented to infant formula, however, not all forms have been available in large scale. The objective of the study was to investigate the dose-dependent effects of an enzymatically-synthesized 6′-sialyllactose (6′-SL) sodium salt supplemented to swine milk replacer on growth, hematological parameters, and organ microscopic assessment in our pre-clinical neonatal pig model. Two-day-old male and female pigs (n = 47) were provided one of four experimental diets for 21 days. Diets were formulated to contain 0 (CON), 300 (LOW), 600 (MOD), or 1200 (HIGH) mg/L of 6′-SL sodium salt. On days 8 and 22, samples were collected for hematological and histological analyses. Supplemental 6′-SL sodium salt at all doses supported growth and development comparable to those observed in control animals. In addition, serum chemistries, hematology, and organ microscopic structure were unaffected by 6′-SL (p > 0.05). Thus, addition of enzymatically-synthesized 6′-SL to a milk replacer formula supported growth and clinical outcomes similar to the control formula in the neonatal piglet.

Toxicological safety assessment of the human-identical milk oligosaccharide 3'-sialyllactose sodium salt.

Human breastmilk is a mixture of nutrients, hormones and bioactive molecules that are vital for infant growth and development. Infant formula (IF) lacks many of these compounds, most notably human milk oligosaccharides (HMOs), which are abundant in breastmilk but scarce in IF. Sialyllactoses, such as 3'-sialyllactose, constitute a large portion of the HMO fraction. To produce IF that matches breastmilk more closely, biosynthesized human-identical milk oligosaccharides (structurally identical to HMOs) such as 3'-sialyllactose sodium salt (3'-SL) are proposed for use in IF and foods for the general population. The safety assessment of 3'-SL comprised in vitro genotoxicity tests and a 90-day oral (gavage) toxicity study. This is the first 90-day study conducted with 3'-SL using neonatal rats (7days old at the start of dosing-equivalent age to newborn human infants in terms of central nervous system and reproductive development), demonstrating the safety of 3'-SL for consumption by infants, the most sensitive age group. The neonatal rats received 3'-SL at doses up to 5,000mg/kg body weight (BW)/day and reference controls received 5,000mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in IF) for comparison with the high-dose 3'-SL group, followed by a 4-week recovery period. There was no evidence of genotoxicity in vitro. In the absence of any test item-related adverse effects in the 90-day study, the high dose (5,000mg/kg BW/day) was established as the no-observed-adverse-effect level. This confirms the safety of 3'-SL for use in IF for infants, as well as in functional foods for the general population.

Toxicological safety evaluation of the human-identical milk oligosaccharide 6'-sialyllactose sodium salt.

Human milk oligosaccharides (HMOs) are abundant in breastmilk, but their presence in infant formula is negligible. Sialylated HMOs, such as 6'-sialyllactose, constitute a significant portion of the HMO fraction of human milk and are linked to important biological functions. To produce infant formula that is more comparable with human milk, biosynthesized sialyllactoses known as human-identical milk oligosaccharides (structurally identical counterparts to their respective naturally occurring HMOs in breastmilk) are proposed for use in infant formula and other functional foods for the general population. To support the safety of 6'-sialyllactose sodium salt (6'-SL), a 90-day oral (gavage) toxicity study and in vitro genotoxicity tests were conducted. The 90-day study is the first to be conducted with 6'-SL using neonatal rats (day 7 of age at the start of dosing), thus addressing safety of 6'-SL for consumption by the most sensitive age group (infants). In the 90-day study, neonatal rats received 6'-SL at doses up to 5000mg/kg body weight (BW)/day and reference controls received 5000mg/kg BW/day of fructooligosaccharide (an ingredient approved for use in infant formula) for comparison with the high-dose 6'-SL group, followed by a 4-week recovery period. There was no evidence of genotoxicity in vitro. No test item-related adverse effects were observed on any parameter in the 90-day study, thus the high dose (5000mg/kg BW/day) was established as the no-observed-adverse-effect level. These results confirm that 6'-SL is safe for use in formula milk for infants and in other functional foods for the general population.

Safety evaluation of 3′-siallylactose sodium salt supplementation on growth and clinical parameters in neonatal piglets

Sialyllactose (SL) is an abundant oligosaccharide in human milk with health benefits that include intestinal maturation, gut microbiota modulation, and cognitive development. Recent technological advances support large scale production of different forms of sialyllactose, which will enable their use as a food ingredient. The objective of the study was to investigate the dose-dependent effects of novel enzymatically-synthesized 3′-sialyllactose (3′SL) sodium salt supplemented to swine milk replacer on growth, hematological parameters and tissue histology in a pre-clinical neonatal pig model. Forty-five two-day-old male and female pigs were provided one of four experimental diets for 21 days. Diets were formulated to contain 0 (CON), 140 (LOW), 200 (MOD) or 500 (HIGH) mg/L of 3′SL sodium salt. Samples were collected on days 8 and 22 of the study for hematological and histological analyses. The addition of 3′SL sodium salt to formula at all doses was well-tolerated by neonatal piglets and supported growth and development comparable to those observed in the CON group. In addition, serum chemistries as well as hematology and organ microscopic structure were unaffected by 3′SL (p > 0.05). These data provide supportive evidence for the safety of supplementation of this enzymatically-synthesized 3′SL sodium salt to human infant formula.

Treatment of Helicobacter pylori infection in rhesus monkeys using a novel antiadhesion compound

Background & Aims: Helicobacter pylori can be eradicated by administration of antimicrobials, but resistant strains have emerged, and there is a need for novel therapeutic approaches against this infection. This study aimed to determine the safety and efficacy of 3'-sialyllactose sodium salt (3'SL), an oligosaccharide that occurs naturally in human and bovine milk and that can inhibit the adhesion of H. pylori to human epithelial cells in vitro. Methods: Twelve H. pylori–positive rhesus monkeys were given 3'SL, either alone (regimens 1 and 2; n = 6) or in combination with omeprazole (regimen 3; n = 4), or bismuth subsalicylate (regimen 4; n = 6). Videogastroscopies were performed before, during, and after treatment, and gastric biopsy specimens were obtained for quantitative cultures and histology. The H. pylori strains colonizing the animals were genotyped. Results: After regimen 1 or 2, 2 of 6 animals were cured permanently, and a third animal was transiently cleared. The 3 other animals remained persistently colonized and did not respond to regimen 3. Regimen 4 resulted in transient decreases in colony counts in 3 of 6 other animals. Gastritis was suppressed only in the 2 animals who became persistently H. pylori negative. There was no apparent relation between 3'SL efficacy and any of the H. pylori tested genotypes. No side effects were observed in any of the animals receiving 3'SL. Conclusions: Antiadhesive therapy is safe; it can cure or decrease H. pylori colonization in some rhesus monkeys, but the addition of a proton pump inhibitor or bismuth subsalicylate does not increase cure rate. GASTROENTEROLOGY 1999;117:1316-1325