Review article

Oligosaccharide anti-infective agents

The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required.

To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs.

This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml).

The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC.

Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ² and Fisher’s exact tests; a p value <0.05 was considered significant.

Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated.

The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs.

Our results show that for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo.

Emerging antimicrobial resistance in infections asks for novel intervention strategies. Galacto-oligosaccharides (GOS) might be attractive alternatives to antibiotics due to their anti-inflammatory and anti-adhesive properties. Mannheimia haemolytica is one of the major Pasteurellaceae associated with bovine lung infections. Using M. haemolytica, we demonstrated that GOS have the capacity to reduce bacterial viability and can be used as adjuvant to improve antibiotic efficacy. Using M. haemolytica-treated primary bronchial epithelial cells (PBECs) of calves, we identified the anti-adhesive and anti-invasive activities of GOS. The observed inhibition of cytokine/chemokine release and the prevention of airway epithelial barrier dysfunction in M. haemolytica-treated PBECs by GOS might be related to the downregulation of “toll-like receptor 4/nuclear factor-κB” pathway and the anti-invasive and anti-adhesive properties of GOS. Particularly, GOS lowered lipopolysaccharides- but not flagellin-induced cytokine/chemokine release in calf and human airway epithelial cells. Finally, we performed in vivo experiments in calves and demonstrated for the first time that intranasal application of GOS can relieve lung infections/inflammation and lower M. haemolytica positivity in the lungs without affecting clinical performance. These findings not only shed light on the anti-inflammatory mechanisms of GOS during lung infections, but GOS might also be a promising anti-bacterial agent for preventing (lung) infections.

Non-digestible oligosaccharides such as milk oligosaccharides (MOS) can regulate and influence immune function. As an example, galactooligosaccharides (GOS), and 2′-fucosyllactose (2′-FL; a specific human MOS) regulate immune development and functionality. Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA), both serious pathogens, can cause severe and life-threatening infections. The aim of this study was to examine the effects of GOS and 2′-FL on bacterial growth and on polymorphonuclear (PMN) phagocytosis.

PMNs were isolated from heparinized whole human blood before treatment/incubation with GOS (0.0625–10%), 2′-FL (0.5–2.5%) and/or GOS combined with 2′-FL (GOS 10%/2′-FL 2.5%; GOS 0.0625%/2′-FL 0.5%) and incubation with green florescent protein (GFP)-labeled SA or PA for 60 h. GFP-relative fluorescent units (GFP-RFU) was measured ≤60 h using a plate reader. Bacterial lag time was determined by the time to onset of exponential bacterial fluorescence/growth alone or after co-culture of bacteria and PMN. Viable bacterial colony-forming units (CFUs) were determined after 60 h.

SA and PA growth lag time was suppressed by co-incubation with GOS in a concentration-dependent manner. This was significant for both SA and PA at concentrations >2.5% GOS (P ≤ 0.05 for both SA and PA) but only for SA at 1% GOS (P ≤ 0.05). 1.5% 2′-FL significantly suppressed the lag time of SA growth (P ≤ 0.05) and was effective against SA and PA at 2.5% (P ≤ 0.01 and P ≤ 0.01, respectively). GOS (10%, 5%) and 2.5% 2′-FL significantly decreased SA and PA bacterial growth/CFUs (P ≤ 0.05).

The data suggests that both GOS and 2′-FL can suppress growth of serious pathogens and enhance phagocytosis.

Oligosaccharides especially prebiotics take high attention in the development of foods because of their physiological properties in human health. They are generally synthetized enzymatically via transferases or hydrolases from mold or bacteria. The fact is that such oligosaccharides synthetized by probiotic bacteria, should be utilized by these microorganisms. This study focused on the production of oligosaccharides with prebiotic potential by crude enzyme preparation from bifidobacteria. Both monosubstrates and bisubstrates systems together with TLC and HPLC techniques, were applied. The crude enzyme preparation has different hydrolase activities such as α-glucosidase (2U/mL), β-glucosidase (0.3 U/mL), α-galactosidase (1.2 U/mL), β-galactosidase (0.4 U/mL), β-fructosidase (11.5 U/mL). Additionally, it also has transglycosylation activities on lactose, lactulose, maltose and sucrose substrates. Two or three types of oligosaccharides were detected. The glycosyltransferase activity peaked at 45 °C, pH 6.6 and 30 g/100 mL substrate concentration. Significant high amount of oligosaccharides were formed in the case of lactose:sucrose combination than others. Both glucooligosaccharides and galactooligosaccharides are detected in the reaction mixtures of bisubstrate. When the lactose is present, the galactosyltransferation is predominated. One-one new types of oligosaccharides were detected in the reaction mixture of bioconversion. Among newly synthetized oligosaccharides, the fraction namely OS4 was utilized by probiotic bifidobacteria only. In conclusion, new types of galacto- and glucooligosaccharides with high prebiotic potentials were synthetized by the crude enzyme from probiotic Bifidobacterium strains.

Sustainable industry practices and circular economy concepts encourage the transformation of production waste into by-products. Saccharomyces cerevisiae is widely used in fermentation industry worldwide, generating large amounts of spent yeast which is mainly directed to animal feed or discarded as waste. Instead of becoming and environmental problem, spent yeast can be directed to the extraction of valuable compounds such as mannans and mannan oligosaccharides (MOS). This review presents a compilation of the studies up to date regarding the different chemical, enzymatic, mechanical or physical processes addressed for mannans extraction and MOS production. Additionally, the existing studies on the chemical modification of mannans aimed to improve specific characteristics are also discussed. Finally, the more relevant bioactivities and potential applications of mannans, MOS and mannose are presented, together with products on the market containing these compounds.

Carbohydrates are an important energy source and play numerous key roles in all living organisms. Carbohydrates chemistry involved in diagnosis and treatment of diseases has been attracting increasing attention. Carbohydrates could be one of the major focuses of new drug discovery. Currently, however, carbohydrate-containing drugs account for only a small percentage of all drugs in clinical use, which does not match the important roles of carbohydrates in the organism. In other words, carbohydrates are a relatively untapped source of new drugs and therefore may offer exciting novel therapeutic opportunities. Here, we presented an overview of the application of carbohydrates in approved small molecule drugs and emphasized and evaluated the roles of carbohydrates in those drugs. The potential development direction of carbohydrate-containing drugs was presented after summarizing the advantages and challenges of carbohydrates in the development of new drugs.