Probiotic strains are claimed to confer health benefits to human organisms when consumed in adequate amounts. Thus, over the last decades there has been an increased interest in the production of functional foods containing probiotic bacteria. However, in order to display optimal probiotic functionality, these bacteria should survive through the gastrointestinal tract (GI) in high populations, reaching 106-107cfu (colony-forming unit)/g or mL at the end of product's shelf life. The food products that can be used as probiotic bacteria carriers exhibit limitations concerning the viability of the cells, associated with parameters such as the acidity of the food matrices or their processing and storage conditions. Moreover, the acid environment of the GI system may be crucial for their survival. Thus, techniques such as microencapsulation and enrichment with prebiotic substances are proposed for their protection. Aim of this review is to present the bacterial strains exhibiting probiotic properties, the microencapsulation techniques which are applied for their protection, as well as their advantages and disadvantages. Finally, the characteristics of the most important food products that have been used as possible matrices for microencapsulated probiotic cells are described.

A review of the microencapsulation techniques for the incorporation of probiotic bacteria in functional foods

Circular bioeconomy and integrated biorefinery in the production of xylooligosaccharides from lignocellulosic biomass: A review

Objective Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration. Design A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays. Results Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway. Conclusion The gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.

Probiotics are live microorganisms that confer health benefits on the host. However, in recent years, several concerns on their use have been raised. In particular, industrial processing and storage of probiotic products are still technological challenges as these could severely impair cell viability. On the other hand, safety of live microorganisms should be taken into account, especially when administered to vulnerable people, such as the elderly and immunodeficient individuals. These drawbacks have enhanced the interest toward new products based on non-viable probiotics such as paraprobiotics and postbiotics. In particular, paraprobiotics, defined as “inactivated microbial cells (non-viable) that confer a health benefit to the consumer,” hold the ability to regulate the adaptive and innate immune systems, exhibit anti-inflammatory, antiproliferative and antioxidant properties and exert antagonistic effect against pathogens. Moreover, paraprobiotics can exhibit enhanced safety, assure technological and practical benefits and can also be used in products suitable for people with weak immunity and the elderly. These features offer an important opportunity to prompt the market with novel functional foods or nutraceuticals that are safer and more stable. This review provides an overview of central issues on paraprobiotics and highlights the urgent need for further studies aimed at assessing safety and efficacy of these products and their mechanisms of action in order to support decisions of regulatory authorities. Finally, a definition is proposed that unambiguously distinguishes paraprobiotics from postbiotics.

https://www.mdpi.com/2072-6643/13/4/1225/pdf

Paraprobiotics: A New Perspective for Functional Foods and Nutraceuticals.

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

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Role of gut microbiota in identification of novel TCM-derived active metabolites.

The roles of newly identified, non-conventional, native gut microbiota bacteria for promotion of health and even therapeutic purposes have rapidly attracted much more attention in contrast to the traditional probiotics. Detailed physiological and molecular evidences on isolation, identification and functional characterization of these various bacteria are rapidly gathering. These potentially beneficial bacteria are gradually grouped to form the next generation probiotics (NGP). Many bacterial species and strains belonging to Actinobacteria, Bacteroidetes, Firmicutes and Verrucomicrobia are gradually highlighted. Notably, NGP may have the potential of being treated as drugs (live biotherapeutic products, LBP); therefore, the requirements for grouping of NGP are much more stringent than traditional probiotics. Comprehensive understandings of effectiveness on amelioration of diseases, safety, physiological, genomic, and metabolomics characteristics, the drug susceptibility pattern and transfer of drug resistance genes, and potential virulence factors are mandatory. Besides, how NPG interact with the host to maintain intestinal integrity and host homeostasis has to be addressed. While most NGP products are currently not commercially available yet, this present review emphasizes the requirements of grouping newly identified microbiota bacteria as NGP. Furthermore, selection of specific functional bacteria to the strain level is essential. We also provide an overview of the potential NGP candidates that could be applied for targeted therapy on specific inflammation related diseases.

Investiture of next generation probiotics on amelioration of diseases – Strains do matter

Antibody immunotherapy is a well-established therapeutic modality for cancer, acute viral infections (Marasco and Sui, 2007) and persistent viral infection such as HIV (Barouch et al., 2013) and HCMV (Freed et al., 2013). To reduce immunogenicity of rodent antibodies (Abs), approved antibody drugs entering clinical trials are of human origin or are humanized versions of rodent antibodies (Reichert, 2008). Recently, there is a strong drive to improve therapeutic efficacy, reduce cost, and provide convenient dosing to patients by designing next-generation antibodies with improved pharmacokinetic properties and modulated immune effector functions (Grevys et al., 2015). The neonatal Fc receptor (FcRn) is a heterodimer that comprises transmembrane α chains and β2-microglubulin (β2m). Optimizing FcRn-IgG interaction through Fc engineering is an effective strategy to improve pharmacokinetic (PK) or pharmacodynamics (PD) properties of therapeutic antibodies (Datta-Mannan et al., 2007). Increased affinity of the FcRn-IgG interaction at pH 6.0 and/or 7.4 has resulted in improved terminal phase halflife (t1/2) of antibodies in vivo (Dall’Acqua et al., 2002). In this study, five Fc variants known to enhance human FcRn (hFcRn) binding with mutations in the CH2 and/or CH3 domains were constructed on a humanized version of E6F6 (huE6F6), a novel therapeutic mAb against HBV. This mAb binds to an unique epitope on HBsAg and potently suppress levels of HBsAg and HBV DNA for several weeks in HBV transgenic mice (Zhang et al., 2016). All five Fc variants showed binding to hFcRn increased by a factor of up to 60-fold at pH 6.0 when compared to wild-type huE6F6 (WT huE6F6). A competitive binding assay was developed to identify the candidate suitable for further pharmacokinetic studies. Finally, huE6F6 Fc mutant M252Y/S254T/T256E (huE6F6-YTE) showed considerably longer serum half-life than the wild-type antibody in both mouse and cynomolgus monkey models. Taken together, these results provide a PKimproved immunotherapeutic agent, the first Fc-modified humanized antibody against chronic HBV infection (CHB). To obtain huE6F6 IgG1 Fc variants with enhanced PK properties, several Fc-engineered variants were made by substitution of amino acid residues at the CH2-CH3 interface, which have been reported to modulate binding to hFcRn, transplacental transport, and serum half-life. Our preliminary results suggested that only these five Fc mutants, T307A/ E380A/N434A (AAA) (Petkova et al., 2006; Yeung et al., 2010), M252Y/S254T/T256E (YTE) (Dall’Acqua et al., 2006; Zalevsky et al., 2010; Robbie et al., 2013), T250Q/M428L (QL) (Hinton et al., 2005), M428L/N434S (LS) (Zalevsky et al., 2010), and N434S (N/S) (Zalevsky et al., 2010) displayed increased level in hFcRn binding compared with WT huE6F6 (data not shown). HBsAg specific chemiluminescent enzyme immunoassay (CLEIA) of titrated Abs showed that these Fc mutants bound equally well to HBsAg, indicating that the Fc mutations had no effect on HBsAg binding (Fig. 1A). As hFcRn binds human IgG (hIgG) at the lower pH of the early endosome (pH 6.0–6.5) and dissociates at the neutral pH of blood (pH 7.4), we established a CLEIA assay to screen antibodies for hFcRn binding at pH 6.0 and pH 7.4, respectively. As expected, hFcRn was shown to bind WT huE6F6 and Fc mutants in a strictly pH-dependent manner, with strong binding at pH 6.0 but reduced interaction at pH 7.4 (Fig. 1B). Furthermore, a side-by-side comparison of the five Fc-engineered variants revealed that they all bound more strongly to hFcRn than did wild-type (WT) by a factor of 4 to 60 at pH 6.0, with a hierarchy from strongest to weakest binding as follows: YTE > LS > N/S > QL > AAA > WT (Fig. 1B). Significant increased level was detected in YTE variant group as compared with WT huE6F6 group (Fig. 1B, P < 0.05). The binding of Fc variants at pH 7.4 were comparably improved with the same ranking of binding affinity as that at pH 6.0 (Fig. 1C). To compare Fc-engineered antibodies and WT huE6F6 in a flow cytometry-based competitive assay of binding to hFcRn at pH 6.0, we constructed a human FcRn-transfected Madin-Darby canine kidney (MDCK) epithelial cell line. Dylight-594 labeled human IgG was used as competitor. Comparison of the IC50 values indicated that the YTE variant with IC50 values of 24.7 μg/mL performed about 40-fold better than did WT huE6F6 in competitive binding to hFcRn at pH 6.0 (Fig. 1D, P < 0.05), which was used in analyzing

/pdf/a-novel-therapeutic-anti-hbv-antibody-with-increased-binding-3cssmmvq06.pdf

Chi-Meng Tzeng

Papers

Role of gut microbiota in identification of novel TCM-derived active metabolites.

Investiture of next generation probiotics on amelioration of diseases – Strains do matter

A novel therapeutic anti-HBV antibody with increased binding to human FcRn improves in vivo PK in mice and monkeys.

Corrigendum to “Investiture of next generation probiotics on amelioration of diseases – Strains do matter” [Med Microecol 1–2 (2019)]