Bifidobacterium adolescentis SBT2786 Improves Sleep Quality in Japanese Adults with Relatively High Levels of Stress: A Randomized, Double-Blind, Placebo-Controlled Study.

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

Bifidobacterium adolescentis-derived hypaphorine alleviates acetaminophen hepatotoxicity by promoting hepatic Cry1 expression.

Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

UPLC/Q-TOF-MS-based metabolomics and molecular docking analysis of Bifidobacterium adolescentis exposure to levofloxacin.

Antibiotic-associated diarrhea is a common adverse reaction caused by the widespread use of antibiotics. The decrease in probiotics is one of the reasons why antibiotics cause drug-induced diarrhea. However, few studies have addressed the intrinsic mechanism of antibiotics inhibiting probiotics. To investigate the underlying mechanism of levofloxacin against Bifidobacterium adolescentis, we used a metabolomics mass spectrometry-based approach and molecular docking analysis for a levofloxacin-induced B. adolescentis injury model. The results showed that levofloxacin reduced the survival rate of B. adolescentis and decreased the number of B. adolescentis. The untargeted metabolomics analysis identified 27 potential biomarkers, and many of these metabolites are involved in energy metabolism, amino acid metabolism and the lipid metabolism pathway. Molecular docking showed that levofloxacin can bind with aminoacyl-tRNA synthetase and lactic acid dehydrogenase. This result provides a novel insight into the mechanism of the adverse reactions of levofloxacin.

Converting Bulk Sugars into Functional Fibers: Discovery and Application of a Thermostable ß-1,3-Oligoglucan Phosphorylase.

Despite their broad application potential, the widespread use of ß-1,3-glucans has been hampered by the high cost and heterogeneity associated with current production methods. To address this challenge, scalable and economically viable processes are needed for the production of ß-1,3-glucans with tailorable molecular mass distributions. Glycoside phosphorylases have shown to be promising catalysts for the bottom-up synthesis of ß-1,3-(oligo)glucans since they combine strict regioselectivity with a cheap donor substrate (i.e., α-glucose 1-phosphate). However, the need for an expensive priming substrate (e.g., laminaribiose) and the tendency to produce shorter oligosaccharides still form major bottlenecks. Here, we report the discovery and application of a thermostable ß-1,3-oligoglucan phosphorylase originating from Anaerolinea thermophila (AtßOGP). This enzyme combines a superior catalytic efficiency toward glucose as a priming substrate, high thermostability, and the ability to synthesize high molecular mass ß-1,3-glucans up to DP 75. Coupling of AtßOGP with a thermostable variant of Bifidobacterium adolescentis sucrose phosphorylase enabled the efficient production of tailorable ß-1,3-(oligo)glucans from sucrose, with a near-complete conversion of >99 mol %. This cost-efficient process for the conversion of renewable bulk sugar into ß-1,3-(oligo)glucans should facilitate the widespread application of these versatile functional fibers across various industries.

Bifidobacterium adolescentis CCFM1285 combined with yeast ß-glucan alleviates the gut microbiota and metabolic disturbances in mice with antibiotic-associated diarrhea.

Antibiotic-associated diarrhea (AAD) is a self-limiting condition that can occur during antibiotic therapy. Our previous studies have found that a combination of Bacteroides uniformis and Bifidobacterium adolescentis can effectively alleviate AAD. However, the use of B. uniformis is still strictly limited. Therefore, this study attempted to use yeast ß-glucan to enrich the abundance of B. uniformis in the intestine and supplement Bifidobacterium adolescentis to exert a synergistic effect. The lincomycin hydrochloride-induced AAD model was administered yeast ß-glucan or a mixture of B. adolescentis CCFM1285 by gavage for one week. Subsequently, changes in the colonic histopathological structure, inflammatory factors, intestinal epithelial permeability and integrity, metabolites, and gut microbiota diversity were assessed. We found that yeast ß-glucan, alone or in combination with B. adolescentis CCFM1285, can help attenuate systemic inflammation, increase the rate of tissue structural recovery, regulate metabolism, and restore the gut microbiota. Specifically, the combination of yeast ß-glucan and B. adolescentis CCFM1285 was more effective in decreasing interleukin-6 levels, improving pathological changes in the colon, and upregulating occludin expression. Therefore, our study showed that the combination of yeast ß-glucan and B. adolescentis CCFM1285 is an efficacious treatment for AAD.

What happens to Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum in an experimental environment with eukaryotic cells?

BACKGROUND: The impact of probiotic strains on host health is widely known. The available studies on the interaction between bacteria and the host are focused on the changes induced by bacteria in the host mainly. The studies determining the changes that occurred in the bacteria cells are in the minority. Within this paper, we determined what happens to the selected Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum in an experimental environment with the intestinal epithelial layer. For this purpose, we tested the bacteria cells' viability, redox activity, membrane potential and enzymatic activity in different environments, including CaCo-2/HT-29 co-culture, cell culture medium, presence of inflammatory inductor (TNF-α) and oxygen. RESULTS: We indicated that the external milieu impacts the viability and vitality of bacteria. Bifidobacterium adolescentis decrease the size of the live population in the cell culture medium with and without TNF-α (p < 0.001 and p < 0.01 respectively). In contrast, Bifidobacterium longum ssp. longum significantly increased survivability in contact with the eukaryotic cells and cell culture medium (p < 0.001). Bifidobacterium adolescentis showed significant changes in membrane potential, which was decreased in the presence of eukaryotic cells (p < 0.01), eukaryotic cells in an inflammatory state (p < 0.01), cell culture medium (p < 0.01) and cell culture medium with TNF-α (p < 0.05). In contrast, Bifidobacterium longum ssp. longum did not modulate membrane potential. Instead, bacteria significantly decreased the redox activity in response to milieus such as eukaryotic cells presence, inflamed eukaryotic cells as well as the culture medium (p < 0.001). The redox activity was significantly different in the cells culture medium vs the presence of eukaryotic cells (p < 0.001). The ability to ß-galactosidase production was different for selected strains: Bifidobacterium longum ssp. longum indicated 91.5% of positive cells, whereas Bifidobacterium adolescentis 4.34% only. Both strains significantly reduced the enzyme production in contact with the eukaryotic milieu but not in the cell culture media. CONCLUSION: The environmental-induced changes may shape the probiotic properties of bacterial strains. It seems that the knowledge of the sensitivity of bacteria to the external environment may help to select the most promising probiotic strains, reduce research costs, and contribute to greater reproducibility of the obtained probiotic effects.

Ecology- and genome-based identification of the Bifidobacterium adolescentis prototype of the healthy human gut microbiota.

Bifidobacteria are among the first microbial colonizers of the human gut, being frequently associated with human health-promoting activities. In the current study, an in silico methodology based on an ecological and phylogenomic-driven approach allowed the selection of a Bifidobacterium adolescentis prototype strain, i.e., B. adolescentis PRL2023, which best represents the overall genetic content and functional features of the B. adolescentis taxon. Such features were confirmed by in vitro experiments aimed at evaluating the ability of this strain to survive in the gastrointestinal tract of the host and its ability to interact with human intestinal cells and other microbial gut commensals. In this context, co-cultivation of B. adolescentis PRL2023 and several gut commensals revealed various microbe-microbe interactions and indicated co-metabolism of particular plant-derived glycans, such as xylan.IMPORTANCEThe use of appropriate bacterial strains in experimental research becomes imperative in order to investigate bacterial behavior while mimicking the natural environment. In the current study, through in silico and in vitro methodologies, we were able to identify the most representative strain of the Bifidobacterium adolescentis species. The ability of this strain, B. adolescentis PRL2023, to cope with the environmental challenges imposed by the gastrointestinal tract, together with its ability to switch its carbohydrate metabolism to compete with other gut microorganisms, makes it an ideal choice as a B. adolescentis prototype and a member of the healthy microbiota of adults. This strain possesses a genetic blueprint appropriate for its exploitation as a candidate for next-generation probiotics.

Mouse intestinal microbiome modulation by oral administration of a GABA-producing Bifidobacterium adolescentis strain.

IMPORTANCE: The gut microbiome-brain communication signaling has emerged in recent years as a novel target for intervention with the potential to ameliorate some conditions associated with the central nervous system. Hence, probiotics with capacity to produce neurotransmitters, for instance, have come up as appealing alternatives to treat disorders associated with disbalanced neurotransmitters. Herein, we further deep into the effects of administering a gamma-aminobutyric acid (GABA)-producing Bifidobacterium strain, previously demonstrated to contribute to reduce serum glutamate levels, in the gut microbiome composition and metabolic activity in a mouse model. Our results demonstrate that the GABA-producing strain administration results in a specific pattern of gut microbiota modulation, different from the one observed in animals receiving non-GABA-producing strains. This opens new avenues to delineate the specific mechanisms by which IPLA60004 administration contributes to reducing serum glutamate levels and to ascertain whether this effect could exert health benefits in patients of diseases associated with high-glutamate serum concentrations.

Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation.

Declined numbers and weakened functions of intestinal stem cells (ISCs) impair the integrity of the intestinal epithelium during aging. However, the impact of intestinal microbiota on ISCs in this process is unclear. Here, using premature aging mice (telomerase RNA component knockout, Terc-/-), natural aging mice, and in vitro colonoid models, we explore how heat-inactivated Bifidobacterium adolescentis (B. adolescentis) affects colon senescence. We find that B. adolescentis could mitigate colonic senescence-related changes by enhancing intestinal integrity and stimulating the regeneration of Lgr5+ ISCs via Wnt/ß-catenin signaling. Furthermore, we uncover the involvement of Paneth-like cells (PLCs) within the colonic stem-cell-supporting niche in the B. adolescentis-induced ISC regeneration. In addition, we identify soluble polysaccharides (SPS) as potential effective components of B. adolescentis. Overall, our findings reveal the role of heat-inactivated B. adolescentis in maintaining the ISCs regeneration and intestinal barrier, and propose a microbiota target for ameliorating colon senescence.

Bifidobacterium adolescentis orchestrates CD143+ cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1.

BACKGROUND: The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated the functional role of Bifidobacterium adolescentis (B.a) on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts (CAFs) in CRC. METHODS: Different CRC animal models and various cell line models were established to explore the function of B.a on CRC. The single-cell RNA sequencing (scRNA-seq) or flow cytometry was used to detect the cell subsets in the TME of CRC. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1 (GAS1) on CD143+ CAFs. Chromatin immunoprecipitation quantitative real-time PCR (CHIP-qPCR) was performed to investigate the regulation of transcription factor 4 (TCF4) on GAS1. Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray. RESULTS: We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo. Supplementation with B.a suppressed ApcMin/+ spontaneous or AOM/DSS-induced tumorigenesis in mice. scRNA-seq revealed that B.a facilitated a subset of CD143+ CAFs by inhibiting the infiltration of Th2 cells, while promoting the TNF-alpha+ B cells in TME. CD143+ CAFs highly expressed GAS1 and exhibited tumor suppressive effect. Mechanistically, GAS1 was activated by the Wnt/ß-catenin signaling in CD143+ CAFs. B.a abundance was correlated with the expression level of CD143 and GAS1. The level of CD143+ CAFs predicted the better survival outcome in CRC patients. CONCLUSIONS: These results highlighted that B.a induced a new subset of CD143+ CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.

Bifidobacterium adolescentis induces Decorin+ macrophages via TLR2 to suppress colorectal carcinogenesis.

BACKGROUND: The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin+ macrophages in colorectal cancer. METHODS: The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin+ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin+ macrophages on the CRC tissue. RESULTS: We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin+ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin+ macrophages and the expression level of TLR2 in tumor tissue of CRC patients. CONCLUSIONS: These results highlight that B. adolescentis induced Decorin+ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.

Orally Administered Bifidobacterium adolescentis Diminishes Serum Glutamate Concentration in Mice.

Several studies have described the contribution of glutamate-transforming microbiota to the development of chronic ailments. For instance, the blood concentration of glutamate is higher in some patients with fibromyalgia, chronic fatigue, and pain. Taking advantage of a naturally occurring strain of Bifidobacterium that is able to transform glutamate in γ-aminobutyric caid (GABA), B. adolescentis IPLA60004, we designed a placebo-controlled intervention to test if the presence of this GABA-producing bifidobacteria in mice was able to impact the concentration of glutamate in the blood in comparison with the administration of other strain of the same species lacking the genes of the glutamate decarboxylase (gad) cluster. Animals were fed every day with 8 log CFU of bacteria in a sterilized milk vehicle for 14 days. Samples from feces and blood were collected during this period, and afterwards animals were sacrificed, tissues were taken from different organs, and the levels of different metabolites were analyzed by ultrahigh-performance liquid chromatography coupled to mass spectrometry. The results showed that both bacterial strains orally administered survived in the fecal content, and animals fed B. adolescentis IPLA60004 showed a significant reduction of their glutamate serum concentration, while a nonsignificant decrease was observed for animals fed a reference strain, B. adolescentis LGM10502. The variations observed in GABA were influenced by the gender of the animals, and no significant changes were observed in different tissues of the brain. These results suggest that orally administered GABA-producing probiotics could reduce the glutamate concentration in blood, opening a case for a clinical trial study in chronic disease patients. IMPORTANCE This work presents the results of a trial using mice as a model that were fed with a bacterial strain of the species B. adolescentis, which possesses different active genes capable of degrading glutamate and converting it into GABA. Indeed, the bacterium is able to survive the passage through the gastric tract and, more importantly, the animals reduce over time the concentration of glutamate in their blood. The importance of this result lies in the fact that several chronic ailments, such as fibromyalgia, are characterized by an increase in glutamate. Our results indicate that an oral diet with this probiotic-type bacteria could reduce the concentration of glutamate and, therefore, reduce the symptoms associated with the excess of this neurotransmitter.

Production of GABA in milk fermented by Bifidobacterium adolescentis strains selected on the bases of their technological and gastrointestinal performance.

There is an increasing interest in producing foods enriched in gamma-aminobutyric acid (GABA), due to their purported health promoting attributes. GABA is the main inhibitor neurotransmitter of the central nervous system, and several microbial species are capable to produce it through decarboxylation of glutamate. Among them, several lactic acid bacteria species have been previously investigated as an appealing alternative to produce GABA enriched foods via microbial fermentation. In this work we report for the first time an investigation into the possibility of utilizing high GABA-producing Bifidobacterium adolescentis strains as a mean to produce fermented probiotic milks naturally enriched in GABA. To this end, in silico and in vitro analyses were conducted in a collection of GABA-producing B. adolescentis strains, with the main goal to scrutinize their metabolic and safety traits, including antibiotic resistance patterns, as well as their technological robustness and performance to survive a simulated gastrointestinal passage. One of the strains, IPLA60004, exhibited better survival to lyophilization and cold storage (for up to 4 weeks at 4 °C), as well as survival to gastrointestinal passage, as compared to the other strains under investigation. Besides, the elaboration of milk drinks fermented with this strain, yielded products with the highest GABA concentration and viable bifidobacterial cell counts, achieving conversion rates of the precursor, monosodium glutamate (GMS), up to 70 %. To our knowledge, this is the first report on the elaboration of GABA enriched milks through fermentation with B. adolescentis.

Polysaccharide BAP1 of Bifidobacterium adolescentis CCDM 368 is a biologically active molecule with immunomodulatory properties.

Bifidobacteria are among the most common bacteria used for their probiotic properties and their impact on the maturation and function of the immune system has been well-described. Recently, scientific interest is shifting from live bacteria to defined bacteria-derived biologically active molecules. Their greatest advantage over probiotics is the defined structure and the effect independent of the viability status of the bacteria. Here, we aim to characterize Bifidobacterium adolescentis CCDM 368 surface antigens that include polysaccharides (PSs), lipoteichoic acids (LTAs), and peptidoglycan (PG). Among them, Bad368.1 PS was observed to modulate OVA-induced cytokine production in cells isolated from OVA-sensitized mice by increasing the production of Th1-related IFN-γ and inhibition of Th2-related IL-5 and IL-13 cytokines (in vitro). Moreover, Bad368.1 PS (BAP1) is efficiently engulfed and transferred between epithelial and dendritic cells. Therefore, we propose that the Bad368.1 PS (BAP1) can be used for the modulation of allergic diseases in humans. Structural studies revealed that Bad368.1 PS has an average molecular mass of approximately 9,99 × 106 Da and it consists of glucose, galactose, and rhamnose residues that are creating the following repeating unit: →2)-ß-D-Glcp-1→3-ß-L-Rhap-1→4-ß-D-Glcp-1→3-α-L-Rhap-1→4-ß-D-Glcp-1→3-α-D-Galp-(1→n.

Metabolomics and molecular docking analysis of antibiotic exposure in Bifidobacterium adolescentis.

Bifidobacterium adolescentis is a probiotic. This research aimed to investigate the mechanism of antibiotics led to decrease in the number of B. adolescentis. The metabolomics approach was employed to explore the effects of amoxicillin on metabolism of B.adolescentis, while MTT assay and scanning electron microscopy were applied to analyse changes in viability and morphology of bacteria. Molecular docking was used to illuminate the mechanism by which amoxicillin acts on a complex molecular network. The results showed that increasing the concentration of amoxicillin led to a gradual decrease in the number of live bacteria. Untargeted metabolomics analysis identified 11 metabolites that change as a result of amoxicillin exposure. Many of these metabolites are involved in arginine and proline metabolism, glutathione metabolism, arginine biosynthesis, cysteine, and methionine metabolism, and tyrosine and phenylalanine metabolism. Molecular docking revealed that amoxicillin had a good binding effect on the proteins AGR1, ODC1, GPX1, GSH, MAT2A, and CBS. Overall, this research provides potential targets for screening probiotic regulatory factors and lays a theoretical foundation for the elucidation of its mechanisms.

The modulation effect of lotus (Nelumbo nucifera Gaertn.) seeds oligosaccharides with different structures on intestinal flora and action mode of growth effects on Bifidobacterium in vivo and in vitro.

Natural lotus seed oligosaccharides monomers (LOSs: LOS3-1, LOS3-2, and LOS4) were prepared by preparative chromatography and were hydroxyl-labeled with fluorescein isothiocyanate (FITC). The prebiotic properties of LOSs by the gut microbiota of male Balb/C mice in vivo and in vitro were studied. In vivo experiment results showed that LOS4 could significantly increase the average daily food consumption, weight, liver index and the abundance of Bacteroides and Bifidobacterium for mice (p < 0.05). In addition, LOS4 also had significant proliferation effect on Bifidobacterium adolescentis and longum in vitro (p < 0.05). Laser confocal microscopy observation showed interaction site between LOS4-FITC and Bifidobacterium adolescentis was located outside and inside of cell, which was completed within 1 h. The relationship between structures of LOSs and prebiotics of intestinal flora (especially Bifidobacterium), and expanded the knowledge on the effects of carbohydrate polymerization degree (DP) and glycosidic bond connection with fermentation selectivity of bacteria was studied.

Regioselective glucosylation of (+)-catechin using a new variant of sucrose phosphorylase from Bifidobacterium adolescentis.

Mutation Q345F in sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) has shown to allow efficient (+)-catechin glucosylation yielding a regioisomeric mixture: (+)-catechin-3'-O-α-D-glucopyranoside, (+)-catechin-5-O-α-D-glucopyranoside and (+)-catechin-3',5-O-α-D-diglucopyranoside with a ratio of 51 : 25 : 24. Here, we efficiently increased the control of (+)-catechin glucosylation regioselectivity with a new variant Q345F/P134D. The same products were obtained with a ratio of 82 : 9 : 9. Thanks to bioinformatics models, we successfully explained the glucosylation favoured at the OH-3' position due to the mutation P134D.

Insights into ß-manno-oligosaccharide uptake and metabolism in Bifidobacterium adolescentis DSMZ 20083 from whole-genome microarray analysis.

Metabolism of non-digestible dietary glycans directly influences the structure and composition of human gut microbiota and, in turn, the host health. ß-Mannans form an integral component of the modern diet as naturally occurring dietary fibre or additives in processed foods. In the present study, in vitro fermentation and TLC studies were used to determine the ability of adult-associated Bifidobacterium adolescentis DSMZ 20083 to utilise ß-manno-oligosaccharides from guar gum, locust bean gum, konjac root, and copra meal generated using GH26 endo-ß-mannanase (ManB-1601). Further, to gain insights into the underlying molecular mechanism, a whole-genome microarray analysis, RT-qPCR, and molecular docking studies were employed to reconstruct the copra meal ß-manno-oligosaccharides (CM-ß-MOS) utilisation pathway in B. adolescentis DSMZ 20083. B. adolescentis DSMZ 20083 grew appreciably (O.D600 nm up to 0.8) on all tested ß-manno-oligosaccharides but maximally on CM-ß-MOS. CM-ß-MOS having DP2-3 were found to deplete from the fermentation media. Whole-genome transcriptome analysis, RT-qPCR, and molecular docking studies suggested that in B. adolescentis DSMZ 20083, ABC & MFS transporters are possibly involved in the uptake of DP ≥ 2 and DP ≥ 3 linear CM-ß-MOS, respectively, while GH1 ß-glucosidase, and GH32 ß-fructofuranosidase possibly cleave linear CM-ß-MOS into monosaccharides. Sugar absorption and utilisation pathways; Bifid shunt, ABC transport system, pyruvate metabolism, glycolysis/gluconeogenesis, pentose, and glucouronate inter-conversions were also found up-regulated following the growth on CM-ß-MOS. This is the first study reporting on possible molecular determinants used by B. adolescentis DSMZ 20083 to utilise ß-manno-oligosaccharides. Our studies can prove resourceful to food and nutraceutical industries, aiming at precision microbiome modulation using ß-manno-oligosaccharides.

Bifidobacterium adolescentis - a beneficial microbe.

Bifidobacterium adolescentis is one of the most abundant bifidobacterial species in the human large intestine, and is prevalent in 60-80% of healthy human adults with cell densities ranging from 109-1010 cells/g of faeces. Lower abundance is found in children and in elderly individuals. The species is evolutionary adapted to fermenting plant-derived glycans and is equipped with an extensive sugar transporter and degradation enzymes repertoire. Consequently, the species is strongly affected by dietary carbohydrates and is able to utilize a wide range of prebiotic molecules. B. adolescentis is specialized in metabolizing resistant starch and is considered a primary starch degrader enabling growth of other beneficial bacteria by cross-feeding. The major metabolic output is acetate and lactate in a ratio of 3:2. Several health-beneficial properties have been demonstrated in certain strains of B. adolescentis in vitro and in rodent models, including enhancement of the intestinal barrier function, anti-inflammatory and immune-regulatory effects, and the production of neurotransmitters (GABA), and vitamins. Although causalities have not been established, reduced abundance of B. adolescentis as part of a dysbiotic colonic microbiota in human observational studies has been associated with inflammatory bowel diseases, irritable bowel syndrome, coeliac disease, cystic fibrosis, Helicobacter pylori infection, type 1 and 2 diabetes, metabolic syndrome, nonalcoholic steatohepatitis, and certain allergies. It is therefore reasonable to conceive B. adolescentis as a health-associated, or even health-promoting bacterial species in humans.

Co-culture fermentations suggest cross-feeding among Bacteroides ovatus DSMZ 1896, Lactiplantibacillus plantarum WCFS1 and Bifidobacterium adolescentis DSMZ 20083 for utilizing dietary galactomannans.

Galactomannans from sources like guar, fenugreek, locust bean, and copra form an important part of human diet. In this study, we have attempted to understand the cross-feeding and resource sharing between a generalist degrader and probiotic utilizers for utilizing dietary galactomannans. In mono-cultures, Bacteroides ovatus DSMZ 1896 grew maximally on substituted galactomannans and produced high amount of succinate. Polysaccharide break down products [ß-manno-oligosaccharides; degree of polymerization (DP) 2-4] left after the growth of B. ovatus DSMZ 1896 in galactomannan supplemented media supported the growth of Lactiplantibacillus plantarum WCFS1 (DP2 and DP3) and Bifidobacterium adolescentis DSMZ 20083 (majorly DP3) and led to the production of lactate and acetate, respectively as the major end products. Co-cultures (bi- and tri-cultures) studies demonstrated cross-feeding being used as a strategy for resource sharing among B. ovatus DSMZ 1896, L. plantarum WCFS1 and B. adolescentis DSMZ 20083 while foraging galactomannans. Structure and DP of galactomannan substrates altered the SCFA and organic acid production patterns in co-cultures.