Non-alcoholic fatty liver disease (NAFLD) is a significant consequence of metabolic dysfunction, often associated with changes in the intestinal microbiota. Prebiotics and probiotics have shown promise in NAFLD management. This study evaluated a silymarin-based herbal remedy with piperine and fulvic acid, alongside a probiotic blend of Bifidobacterium adolescentis, Bifidobacterium bifidum, Lactobacillus casei, and Lactobacillus rhamnosus. Using a NAFLD mouse model induced by a high-fat and high-fructose diet, we assessed biochemical parameters, liver function, glucose levels, and conducted histological analysis. Stool samples underwent 16S rRNA metagenomic analysis to explore changes in microbiota composition. Mice on the high-fat diet exhibited elevated lipids, liver enzymes, and glucose, with reduced high-density lipoprotein levels (with p value < 0.001). Treatment, particularly with F3 (silymarin-piperine-fulvic acid herbal remedy and probiotic blend), significantly reduced hepatic fat accumulation and improved gut microbiota composition. This study highlights the potential of silymarin-based therapy combined with probiotics in attenuating NAFLD progression.

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.

Serum-derived bovine immunoglobulin (SBI) prevents translocation and inflammation via direct binding of microbial components. Recently, SBI also displayed potential benefits through gut microbiome modulation. To confirm and expand upon these preliminary findings, SBI digestion and colonic fermentation were investigated using the clinically predictive ex vivo SIFR® technology (for 24 human adults) that was, for the first time, combined with host cells (epithelial/immune (Caco-2/THP-1) cells). SBI (human equivalent dose (HED) = 2 and 5 g/day) and the reference prebiotic inulin (IN; HED = 2 g/day) significantly promoted gut barrier integrity and did so more profoundly than a dietary protein (DP), especially upon LPS-induced inflammation. SBI also specifically lowered inflammatory markers (TNF-α and CXCL10). SBI and IN both enhanced SCFA (acetate/propionate/butyrate) via specific gut microbes, while SBI specifically stimulated valerate/bCFA and indole-3-propionic acid (health-promoting tryptophan metabolite). Finally, owing to the high-powered cohort (n = 24), treatment effects could be stratified based on initial microbiota composition: IN exclusively stimulated (acetate/non-gas producing) Bifidobacteriaceae for subjects classifying as Bacteroides/Firmicutes-enterotype donors, coinciding with high acetate/low gas production and thus likely better tolerability of IN. Altogether, this study strongly suggests gut microbiome modulation as a mechanism by which SBI promotes health. Moreover, the SIFR® technology was shown to be a powerful tool to stratify treatment responses and support future personalized nutrition approaches.

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.

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.

Despite their broad application potential, the widespread use of β-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 β-1,3-glucans with tailorable molecular mass distributions. Glycoside phosphorylases have shown to be promising catalysts for the bottom-up synthesis of β-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 β-1,3-oligoglucan phosphorylase originating from Anaerolinea thermophila (AtβOGP). This enzyme combines a superior catalytic efficiency toward glucose as a priming substrate, high thermostability, and the ability to synthesize high molecular mass β-1,3-glucans up to DP 75. Coupling of AtβOGP with a thermostable variant of Bifidobacterium adolescentis sucrose phosphorylase enabled the efficient production of tailorable β-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 β-1,3-(oligo)glucans should facilitate the widespread application of these versatile functional fibers across various industries.

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 β-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 β-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 β-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 β-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 β-glucan and B. adolescentis CCFM1285 is an efficacious treatment for AAD.

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 β-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.
CONCLUSIONS: 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.

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.

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.