Co-culturing Propionibacterium freudenreichii and Bifidobacterium animalis subsp. lactis improves short-chain fatty acids and vitamin B12 contents in soy whey.

The lack of vitamin B12 in unprocessed plant-based foods can lead to health problems in strict vegetarians and vegans. The main aim of this study was to investigate the potential synergy of co-culturing Bifidobacterium animalis subsp. lactis and Propionibacterium freudenreichii in improving production of vitamin B12 and short-chain fatty acids in soy whey. Different strategies including mono-, sequential and simultaneous cultures were adopted. Growth, short-chain fatty acids and vitamin B12 were assessed throughout the fermentation while free amino acids, volatiles, and isoflavones were determined on the final day. P. freudenreichii monoculture grew well in soy whey, whereas B. lactis monoculture entered the death phase by day 4. Principal component analysis demonstrates that metabolic changes in both sequential cultures did not show drastic differences to those of P. freudenreichii monoculture. However, simultaneous culturing significantly improved vitamin B12, acetic acid and propionic acid contents (1.3 times, 5 times, 2.5 times, compared to the next highest treatment [sequential cultures]) in fermented soy whey relative to other culturing modes. Hence, co-culturing of P. freudenreichii and B. lactis would provide an alternative method to improve vitamin B12, acetic acid and propionic acid contents in fermented foods.

Stabilization by Chaperone GroEL in Biogenic Selenium Nanoparticles Produced from Bifidobacterium animalis H15 for the Treatment of DSS-Induced Colitis.

Inflammatory bowel diseases have a high rate of mortality and pose a serious threat to global public health. Selenium is an essential trace element, which has been shown to play important roles in redox control and antioxidant defense. Microorganisms play important roles in the reduction of toxic inorganic selenium (selenite and selenate) to less-toxic biogenic selenium nanoparticles (Bio-SeNPs), which have higher biocompatibility. In the present study, novel Bio-SeNPs with high stability were synthesized using probiotic Bifidobacterium animalis subsp. lactis H15, which was isolated from breastfed infant feces. The Bio-SeNPs with a size of 122 nm showed stability at various ionic strengths, temperatures, and in simulated gastrointestinal fluid, while chemosynthetic SeNPs underwent aggregation. The main surface protein in the Bio-SeNPs was identified as chaperone GroEL by liquid chromatography-tandem mass spectrometry. The overexpression and purification of GroEL demonstrated that GroEL controlled the assembly of Bio-SeNPs both in vitro and in vivo. In vivo, oral administration of Bio-SeNPs could alleviate dextran sulfate sodium-induced colitis by decreasing cell apoptosis, increasing antioxidant capacity and the number of proliferating cells, and improving the function of the intestinal mucosal barrier. In vitro experiments verified that Bio-SeNPs inhibited lipopolysaccharide-induced toll-like receptor 4/NF-κB signaling pathway activation. These results suggest that the Bio-SeNPs with high stability could have potential as a nutritional supplement for the treatment of colitis in nanomedicine applications.

Bifidobacterium improves oestrogen-deficiency-induced osteoporosis in mice by modulating intestinal immunity.

Osteoporosis has become one of the major diseases that threaten the health of middle-aged and elderly people, and with the growth of an ageing population, more and more people are affected by osteoporosis these days. In recent years, intestinal flora has been found to affect the host immune system, and an overactive immune system is closely related to bone resorption. Probiotics can effectively improve bone density and strength, reduce bone loss, and improve osteoporosis, but their mechanism of action and relationship with intestinal microbiota are still unclear. In this study, two strains of Bifidobacterium (Bifidobacterium bifidum FL228.1 and Bifidobacterium animalis subsp. Lactis F1-7) that can alleviate intestinal inflammation were screened based on previous experiments. Through the construction of an ovariectomized mouse model, the improvement of osteoporosis by Bifidobacterium was detected, and the influence of Bifidobacterium on intestinal immunity was explored. The results show that Bifidobacterium treatment significantly improved bone mineral density (BMD), bone volume/total volume ratio (BV/TV), and trabecular number (Tb·N), and effectively suppressed bone loss. Furthermore, Bifidobacterium treatment could inhibit the expression of inflammatory cytokines in the gut, alleviate gut inflammation, and thus suppress excessive osteoclast generation. Its mechanism of action includes factors that protect the mucosal barrier, including occludin, ZO-1, claudin-2, and MUC2, and the reduction of pro-inflammatory M1 macrophages. B. bifidum FL228.1 increased the abundance of beneficial bacteria in the colon, including Lactobacillus and Colidextribacter. B. animalis F1-7 increased the abundance of Bifidobacterium and decreased the abundance of Desulfovibrio and Ruminococcus in the colon. These research findings expand our understanding of the gut-bone axis and provide new guidance for the development of probiotic-based therapies for osteoporosis in the future.

Bifidobacterium animalis subsp. lactis Probio-M8 alleviates abnormal behavior and regulates gut microbiota in a mouse model suffering from autism.

Probiotics can effectively improve a variety of neurological diseases, but there is little research on autism, and the specific mechanism is unclear. In this study, shotgun metagenomics analysis was used to investigate the preventive and therapeutic effects of Bifidobacterium animalis subsp. lactis Probio-M8 on autism. The results showed that Probio-M8 treatment significantly alleviated valproate (VPA)-induced autism in mice, with autistic symptoms characterized by increased stereotyped behaviors such as grooming, reduced learning ability, and decreased desire to socialize. Further studies have found that Probio-M8 can alleviate autism by optimizing gut microbiota diversity and regulating metabolic levels. Probio-M8 regulates gut microbiota structure by increasing the abundance of beneficial bacteria such as Bifidobacterium globosum and Akkermansia muciniphila. In addition, Probio-M8 regulates metabolic activity by increasing levels of choline, which corrects CAZy disorders. In conclusion, Probio-M8 is therapeutic in the VPA-induced autism mouse model by regulating the gut microbiome and metabolic levels.IMPORTANCEIndividuals with autism often exhibit symptoms of social invariance, obsessive-compulsive tendencies, and repetitive behaviors. However, early intervention and treatment can be effective in improving social skills and mitigating autism symptoms, including behaviors related to irritability. Although taking medication for autism may lead to side effects such as weight gain, probiotics can be an ideal intervention for alleviating these symptoms. In this study, we investigated the effects of Probio-M8 intervention on the behavior of autistic mice using an open-field test, a three-chamber sociability test, and a novel object recognition test. Metagenomic analysis revealed differences in gut microbiota diversity among groups, predicted changes in metabolite levels, and functionally annotated CAZy. Additionally, we analyzed serum neurotransmitter levels and found that probiotics were beneficial in mitigating neurotransmitter imbalances in mice with autism.

Bioavailability of Macroelements from Synbiotic Sheep's Milk Ice Cream.

To determine the potential bioavailability of macroelements (Ca, Mg, P, K), probiotic ice cream samples (Lactaseibacillus paracasei L-26, Lactobacillus casei 431, Lactobacillus acidophilus LA-5, Lactaseibacillus rhamnosus and Bifidobacterium animalis ssp. lactis BB-12) from sheep's milk with inulin, apple fiber and inulin, or apple fiber and control samples were submitted to in vitro digestion in the mouth, stomach and small intestine. The bioavailability of calcium in the ice cream samples ranged from 40.63% to 54.40%, whereas that of magnesium was 55.64% to 44.42%. The highest bioavailability of calcium and magnesium was shown for the control samples. However, adding 4% inulin reduced the bioavailability of calcium by about 3-5% and magnesium only by about 5-6%. Adding 4% apple fiber reduced the bioavailability of calcium by as much as 6-12% and magnesium by 7-8%. The highest bioavailability of calcium was determined in ice cream with L. paracasei, and the highest bioavailability of magnesium was determined in ice cream with L. casei. The bioavailability of phosphorus in ice cream ranged from 47.82% to 50.94%. The highest bioavailability of phosphorus (>50%) was in sheep ice cream fermented by B. animalis. In the control ice cream, the bioavailability of potassium was about 60%. In ice cream with inulin, the bioavailability of potassium was lower by 3-4%, and in ice cream with apple fiber, the bioavailability of potassium was lower by up to 6-9%. The bioavailability of potassium was significantly influenced only by the addition of dietary fiber. The results of the study confirmed the beneficial effect of bacteria on the bioavailability of Ca, Mg and P.

In Vitro Probiotic Properties of Bifidobacterium animalis subsp. lactis SF and Its Alleviating Effect on Non-Alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with many influencing factors. With the increasing role of the gut-liver axis in various liver diseases, research on the prevention and treatment of NAFLD with probiotics is increasing. In the present study, a Bifidobacterium animalis subsp. strain, B. lactis SF, was isolated from the feces of healthy infants and characterized by sequencing of the 16S rDNA. A systematic probiotic evaluation was carried out, and a diet-induced mouse model was constructed to study the effect and mechanism of B. lactis SF on diet-induced NAFLD. Results show that B. lactis SF has excellent gastrointestinal fluid tolerance and intestinal colonization, and strong antibacterial and antioxidant capabilities. In vivo, B. lactis SF modulated intestinal flora, restored the intestinal barrier, and inhibited LPS entrance into the portal circulation, which subsequently inhibited the TLR4/NF-κB and modulated the PI3K-Akt/AMPK signaling pathway, attenuated the inflammatory response, and reduced lipid accumulation. In addition, B. lactis SF attenuated oxidative stress and further alleviated autophagy, resulting in an ameliorative effect on NAFLD. Therefore, our study provides a new dietary method for the treatment of NAFLD.

Bifidobacterium animalis subsp. lactis BL-99 ameliorates colitis-related lung injury in mice by modulating short-chain fatty acid production and inflammatory monocytes/macrophages.

Pulmonary inflammation as one of the extraintestinal manifestations of ulcerative colitis (UC) has attracted extensive attention, and its pathogenesis is closely related to gut dysbiosis. Bifidobacterium animalis subsp. lactis BL-99 (BL-99) can alleviate osteoporosis caused by UC, but less research has been done on other extraintestinal manifestations (EIM) caused by UC. This study aimed to explore the role and potential mechanisms of BL-99 on DSS-induced pulmonary complications in colitis mice. The results showed that BL-99 decreased weight loss, disease activity index score, colonic pathology score, and the production of pro-inflammatory cytokines (e.g., TNF-α, IL-1ß, and IL-6) in colitis mice. BL-99 also alleviated DSS-induced lung pathological damage by suppressing the infiltration of pro-inflammatory cytokines, inflammatory monocytes, and macrophages. Furthermore, 16S rRNA gene sequencing showed lower abundances of several potentially pathogenic bacteria (e.g., Burkholderia, Shigella, and Clostridium perfringens) and enrichment in specific beneficial bacteria (e.g., Adlercreutzia and Bifidobacterium animalis) in colitis mice with BL-99 treatment. Targeted metabolomics suggested that BL-99 intervention promoted the production of intestinal acetate and butyrate. Finally, we observed that the pulmonary expression of primary acetate and butyrate receptors, including FFAR2, FFAR3, and, GPR109a, was up-regulated in BL-99-treated mice, which negatively correlated with inflammatory monocytes and macrophages. Altogether, these results suggest that BL-99 might be utilized as a probiotic intervention to prevent the incidence of colitis-related lung injury owing to its ability to shape the intestinal microbiota and suppress inflammation.

Chronic Treatment with the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium lactis BB12 Attenuates Motor Impairment, Striatal Microglial Activation, and Dopaminergic Loss in Rats with 6-Hydroxydopamine-induced Hemiparkinsonism.

Gut dysbiosis is considered a risk factor for Parkinson's disease (PD), and chronic treatment with probiotics could prevent it. Here we report the assessment of a probiotic mixture [Lacticaseibacillus rhamnosus GG (LGG), and Bifidobacterium animalis lactis BB-12 (BB-12)] administered to male rats 2 weeks before and 3 weeks after injecting 6-hydroxydopamine (6-OHDA) into the right striatum, a model that mimics the early stages of PD. Before and after lesion, animals were subjected to behavioral tests: narrow beam, cylinder test, and apomorphine (APO)-induced rotations. Dopaminergic (DA) denervation and microglia recruitment were assessed with tyrosine hydroxylase (TH+) and ionized calcium-binding protein-1 adapter (Iba1+) immunostaining, respectively. Post 6-OHDA injury, rats treated with sunflower oil (probiotics vehicle) developed significant decrease in crossing speed and increases in contralateral paw slips (narrow beam), forepaw use asymmetry (cylinder), and APO-induced rotations. In striatum, 6-OHDA eliminated ≈2/3 of TH+ area and caused significant increase of Iba1+ microglia population. Retrograde axonal degeneration suppressed ≈2/5 of TH+ neurons in the substantia nigra pars compacta (SNpc). In hemiparkinsonian rats, probiotics treatment significantly improved the crossing speed, and also reduced paw slips (postlesion days 14 and 21), the loss of TH+ neurons in SNpc, and the loss of TH+ area and of Iba1+ microglia count in striatum, without affecting the proportion of microglia morphological phenotypes. Probiotics treatment did not attenuate forepaw use asymmetry nor APO-induced rotations. These results indicate that the mixture of probiotics LGG and BB-12 protects nigrostriatal DA neurons against 6-OHDA-induced damage, supporting their potential as preventive treatment of PD.

Bifidobacterium animalis Promotes the Growth of Weaning Piglets by Improving Intestinal Development, Enhancing Antioxidant Capacity, and Modulating Gut Microbiota.

Probiotics are widely used to promote performance and improve gut health in weaning piglets. Therefore, the objective of this study was to investigate the effects of dietary supplementation with Bifidobacterium animalis subsp. lactis (B. animalis) JYBR-190 on the growth performance, intestine health, and gut microbiota of weaning piglets. The results showed that the dietary addition of B. animalis significantly improved growth performance and decreased diarrhea incidence. B. animalis increased villus height in the duodenum and elevated goblet cell numbers and amylase activity in the jejunum. Additionally, B. animalis supplementation markedly increased total antioxidant capacity in jejunal mucosa but declined the malondialdehyde content. B. animalis treatment did not affect the mRNA expressions associated with the intestinal barrier and inflammatory cytokine in various intestinal segments. Microbiota analysis indicated that a diet supplemented with B. animalis significantly increased the relative abundances of health-promoting bacteria in the lumen, such as Streptococcus, Erysipelotrichaceae, Coprococcus, and Oscillibacter. There was a trend for B. animalis fed piglets to have a higher relative abundance of B. animalis in ileal digesta. Moreover, B. animalis-treated pigs decreased the abundance of Helicobacter and Escherichia-Shigella in ileal mucosa-associated microbiota. In summary, this study showed that B. animalis supplementation stimulated growth performance, improved gut development, enriched beneficial bacteria abundances, and declined intestinal pathogens populations, while B. animalis had limited effects on the intestinal barrier and immune function. IMPORTANCE In the modern swine industry, weaning is a critical period in the pig's life cycle. Sudden dietary, social, and environmental changes can easily lead to gut microbiota dysbiosis, diarrhea, and a decrease in growth performance. To stabilize intestinal microbiota and promote animal growth, antibiotics were widely applied in swine diets during the past few decades. However, the side effects of antibiotics posed a great threat to public health and food safety. Therefore, it is urgent to find and develop antibiotic alternatives. The growing evidence suggested that probiotics can be preferable alternatives to antibiotics because they can modulate microbiota composition and resist pathogens colonization. In this study, our results indicated that dietary supplementation with Bifidobacterium animalis promoted growth in weaning piglets by improving gut development, increasing beneficial bacteria abundances, and declining pathogens populations.

Probiotic Bifidobacterium animalis ssp. lactis Probio-M8 improves the properties and organic acid metabolism of fermented goat milk.

The addition of Bifidobacterium to goat milk has dual effects on health, for which various inherent nutrients of goat milk are retained and live probiotics are provided. We explored the effect of Bifidobacterium animalis ssp. lactis Probio-M8 (Probio-M8) on fermentation characteristics, formation of organic acid, sensory properties, and storage characteristics of fermented goat milk (with added 4.0% sucrose). Addition of Probio-M8 decreased the fermentation time and significantly increased the content of functional organic acids, such as acetic acid, and functional long-chain unsaturated fatty acids, including linoleic acid, α-linolenic acid, and docosahexaenoic acid. Furthermore, the contents of medium-chain and short-chain fatty acids, which are related to "goaty" flavor, were significantly lower in the Probio-M8 treatment compared with the control. The number of living Probio-M8 decreased from 8.27 log cfu/mL (1.80 × 108 cfu/mL) to 7.94 log cfu/mL (0.79 × 108 cfu/mL) after 28 d of storage. Titratable acidity and pH value did not differ between the control group and experimental group (containing Probio-M8). Sensory evaluation indicated a lower goaty flavor and odor in the Probio-M8 fermented milk. Our results suggest that the addition of the probiotic Probio-M8 could improve the sensory, physicochemical, and functional properties of fermented goat milk.

Effect of the addition of the probiotic Bifidobacterium animalis subsp. Lactis (BB-12) in free and microencapsulated form and the prebiotic inulin to synbiotic dry coppa.

The effect of the addition of the prebiotic inulin and free and microencapsulated Bifidobacterium animalis subsp. Lactis (BB-12) strains to synbiotic dry coppa formulations was evaluated during 45 days of ripening. The following formulations were made: control C without probiotic and prebiotic; PROB with free probiotic; SYNB with free probiotic and inulin; ENPROB with microencapsulated probiotic, and ENSYNB with microencapsulated probiotic and inulin. The incorporation of BB-12 with inulin provided adequate physicochemical characteristics (proximate composition, weight loss, pH, water activity (aw), and instrumental color). The treatments PRO and SYNB showed lower lipid and protein oxidation levels. The treatments PROB, SYNB, ENPROB, and ENSYNB had viable cell counts above 109 CFU/g and can be considered probiotic. In the in vitro gastrointestinal simulation, the BB-12 strain showed survival and growth capacity in saline solution and at low pH values for all treatments. The sample SYNB was the most accepted by the assessors in the sensory evaluation. Therefore, dry coppa can be used as a vehicle for the development of a synbiotic fermented meat product.

Intake of Bifidobacterium lactis Probio-M8 fermented milk protects against alcoholic liver disease.

Alcoholic liver disease (ALD) is a liver disease caused by long-term heavy drinking, which is characterized by increased inflammation and oxidative stress in the liver and gut dysbiosis. The purpose of this study was to investigate the protective effect of administering ordinary and probiotic- (containing the Bifidobacterium animalis ssp. lactis Probio-M8 strain; M8) fermented milk to rats. Several biochemical parameters and the fecal metagenomes were monitored before (d 0) and after (d 42) the intervention. Our results confirmed that alcohol could cause significant changes in the liver levels of the proinflammatory cytokine IL-1ß, antioxidation indicators, and liver function-related indicators; meanwhile, the gut bacterial and viral microbiota were disrupted with significant reduction in microbial diversity and richness. Feeding the rats with Probio-M8-fermented milk effectively maintained the gut microbiota stability, reduced liver inflammation and oxidative stress, and mitigated liver damages in ALD. Moreover, the Probio-M8-fermented milk reversed alcohol-induced dysbiosis by restoring the gut microbiota diversity, richness, and composition. Four predicted fecal metabolites (inositol, tryptophan, cortisol, and vitamin K2) increased after the intervention, which might help regulate liver metabolism and alleviate ALD-related symptoms. In short, our data supported that consuming Probio-M8-fermented milk effectively mitigated ALD. The protective effect against ALD could be related to changes in the gut microbiome after probiotic-fermented milk consumption. However, such observation and the causal relationship among probiotic milk consumption, changes in gut microbiome, and disease alleviation would still need to be further confirmed. Nevertheless, this study has shown in a rat model that consuming probiotic-fermented milk could protect against ALD.

Ameliorative Effects of Bifidobacterium animalis subsp. lactis J-12 on Hyperglycemia in Pregnancy and Pregnancy Outcomes in a High-Fat-Diet/Streptozotocin-Induced Rat Model.

Bifidobacterium, a common probiotic, is widely used in the food industry. Hyperglycemia in pregnancy has become a common disease that impairs the health of the mother and can lead to adverse pregnancy outcomes, such as preeclampsia, macrosomia, fetal hyperinsulinemia, and perinatal death. Currently, Bifidobacterium has been shown to have the potential to mitigate glycolipid derangements. Therefore, the use of Bifidobacterium-based probiotics to interfere with hyperglycemia in pregnancy may be a promising therapeutic option. We aimed to determine the potential effects of Bifidobacterium animalis subsp. lactis J-12 (J-12) in high-fat diet (HFD)/streptozotocin (STZ)-induced rats with hyperglycemia in pregnancy (HIP) and respective fetuses. We observed that J-12 or insulin alone failed to significantly improve the fasting blood glucose (FBG) level and oral glucose tolerance; however, combining J-12 and insulin significantly reduced the FBG level during late pregnancy. Moreover, J-12 significantly decreased triglycerides and total cholesterol, relieved insulin and leptin resistance, activated adiponectin, and restored the morphology of the maternal pancreas and hepatic tissue of HIP-induced rats. Notably, J-12 ingestion ameliorated fetal physiological parameters and skeletal abnormalities. HIP-induced cardiac, renal, and hepatic damage in fetuses was significantly alleviated in the J-12-alone intake group, and it downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health. Furthermore, placental tissue damage in rats with HIP appeared to be in remission in the J-12 group. Upon exploring specific placental microbiota, we observed that J-12 affected the abundance of nine genera, positively correlating with FBG and leptin in rats and hippocampal mRNA levels of InsR and IGF-1R mRNA in the fetus, while negatively correlating with adiponectin in rats and hippocampal levels of AKT in the fetus. These results suggest that J-12 may affect the development of the fetal central nervous system by mediating placental microbiota via the regulation of maternal-related indicators. J-12 is a promising strategy for improving HIP and pregnancy outcomes.

The use of probiotics can reduce the severity of experimental periodontitis in rats with metabolic syndrome: An immunoenzymatic and microtomographic study.

BACKGROUND: This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) in rats. METHODS: Ninety-six rats were grouped according to a food protocol: high-fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) probiotic (PROB): C-**, CP-*, PE+**, PEP+*, MS- MSP-*, MSPE+**, and MSPEP+*. PROB administration started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (P < 0.05). RESULTS: The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared with the PE and MSPE groups, respectively (P < 0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)-1ß and a higher receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio in the MSPE group when compared with the MSPEP group (P < 0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)-α and IL-6 when compared with the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE. CONCLUSION: B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues.

Adjunctive Probiotics Alleviates Asthmatic Symptoms via Modulating the Gut Microbiome and Serum Metabolome.

Asthma is a multifactorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics have shown anti-inflammatory effects and could regulate the gut-lung axis. Thus, a 3-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma. Fifty-five asthmatic patients were randomly assigned to a probiotic group (n = 29; received Bifidobacterium lactis Probio-M8 powder and Symbicort Turbuhaler) and a placebo group (n = 26; received placebo and Symbicort Turbuhaler), and all 55 subjects provided details of their clinical history and demographic data. However, only 31 patients donated a complete set of fecal and blood samples at all three time points for further analysis. Compared with those of the placebo group, co-administering Probio-M8 with Symbicort Turbuhaler significantly decreased the fractional exhaled nitric oxide level at day 30 (P = 0.049) and improved the asthma control test score at the end of the intervention (P = 0.023). More importantly, the level of alveolar nitric oxide concentration decreased significantly among the probiotic receivers at day 30 (P = 0.038), and the symptom relief effect was even more obvious at day 90 (P = 0.001). Probiotic co-administration increased the resilience of the gut microbiome, which was reflected by only minor fluctuations in the gut microbiome diversity (P > 0.05, probiotic receivers; P < 0.05, placebo receivers). Additionally, the probiotic receivers showed significantly changes in some species-level genome bins (SGBs), namely, increases in potentially beneficial species Bifidobacterium animalis, Bifidobacterium longum, and Prevotella sp. CAG and decreases in Parabacteroides distasonis and Clostridiales bacterium (P < 0.05). Compared with that of the placebo group, the gut metabolic potential of probiotic receivers exhibited increased levels of predicted microbial bioactive metabolites (linoleoyl ethanolamide, adrenergic acid, erythronic acid) and serum metabolites (5-dodecenoic acid, tryptophan, sphingomyelin) during/after intervention. Collectively, our results suggested that co-administering Probio-M8 synergized with conventional therapy to alleviate diseases associated with the gut-lung axis, like asthma, possibly via activating multiple anti-inflammatory pathways. IMPORTANCE The human gut microbiota has a potential effect on the pathogenesis of asthma and is closely related to the disease phenotype. Our trial has demonstrated that co-administering Probio-M8 synergized with conventional therapy to alleviate asthma symptoms. The findings of the present study provide new insights into the pathogenesis and treatment of asthma, mechanisms of novel therapeutic strategies, and application of probiotics-based therapy.

Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome.

The administration of broad-spectrum antibiotics is often associated with antibiotic-associated diarrhea (AAD), and impacts gastrointestinal tract homeostasis, as evidenced by the following: (a) an overall reduction in both the numbers and diversity of the gut microbiota, and (b) decreased short-chain fatty acid (SCFA) production. Evidence in humans that probiotics may enhance the recovery of microbiota populations after antibiotic treatment is equivocal, and few studies have addressed if probiotics improve the recovery of microbial metabolic function. Our aim was to determine if Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-containing yogurt could protect against antibiotic-induced fecal SCFA and microbiota composition disruptions. We conducted a randomized, allocation-concealed, controlled trial of amoxicillin/clavulanate administration (days 1-7), in conjunction with either BB-12-containing or control yogurt (days 1-14). We measured the fecal levels of SCFAs and bacterial composition at baseline and days 7, 14, 21, and 30. Forty-two participants were randomly assigned to the BB-12 group, and 20 participants to the control group. Antibiotic treatment suppressed the fecal acetate levels in both the control and probiotic groups. Following the cessation of antibiotics, the fecal acetate levels in the probiotic group increased over the remainder of the study and returned to the baseline levels on day 30 (-1.6% baseline), whereas, in the control group, the acetate levels remained suppressed. Further, antibiotic treatment reduced the Shannon diversity of the gut microbiota, for all the study participants at day 7. The magnitude of this change was larger and more sustained in the control group compared to the probiotic group, which is consistent with the hypothesis that BB-12 enhanced microbiota recovery. There were no significant baseline clinical differences between the two groups. Concurrent administration of amoxicillin/clavulanate and BB-12 yogurt, to healthy subjects, was associated with a significantly smaller decrease in the fecal SCFA levels and a more stable taxonomic profile of the microbiota over time than the control group.

Effect of a Probiotic Supplement Containing Lactobacillus Acidophilus and Bifidobacterium Animalis Lactis on Urine Oxalate in Calcium Stone Formers with Hyperoxaluria: A Randomized, Placebo-controlled, Double-blind and In-vitro Trial.

PURPOSE: To determine the effect of a probiotic supplement containing native Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium animalis lactis (B. lactis) on 24-hour urine oxalate in recurrent calcium stone formers with hyperoxaluria. Moreover, the in-vitro oxalate degradation capacity and the intestinal colonization of consumed probiotics were evaluated. MATERIALS AND METHODS: The oxalate degrading activity of L. acidophilus and B. lactis were evaluated in-vitro. The presence of oxalyl-CoA decarboxylase (oxc) gene in the probiotic species was assessed. One hundred patients were randomized to receive the probiotic supplement or placebo for four weeks. The 24-hour urine oxalate and the colonization of consumed probiotics were assessed after weeks four and eight. RESULTS: Although the oxc gene was present in both species, only L. acidophilus had a good oxalate degrading activity, in-vitro. Thirty-four patients from the probiotic and thirty patients from the placebo group finished the study. The urine oxalate changes were not significantly different between groups (57.21 ± 11.71 to 49.44 ± 18.14 mg/day for probiotic, and 56.43 ± 9.89 to 50.47 ± 18.04 mg/day for placebo) (P = .776). The probiotic consumption had no significant effect on urine oxalate, both in univariable (P = .771) and multivariable analyses (P = .490). The consumed probiotics were not detected in the stool samples of most participants. CONCLUSION: Our results showed that the consumption of a probiotic supplement containing L. acidophilus and B. lactis did not affect urine oxalate. The results may be due to a lack of bacterial colonization in the intestine.

Different effects of soybean protein and its derived peptides on the growth and metabolism of Bifidobacterium animalis subsp. animalis JCM 1190.

Bifidobacterium is a common probiotic that plays a vital role in the intestinal tract. This study aimed to explore the different effects of soybean protein and soybean peptides on the growth and metabolism of Bifidobacterium animalis subsp. animalis JCM 1190. Soybean protein and soybean peptides were digested in vitro, after which different nitrogen source containing media were prepared and used for the monoculture of Bifidobacterium animalis subsp. animalis JCM 1190 and the co-culture of Bifidobacterium animalis subsp. animalis JCM 1190 and Escherichia coli JCM 1649. During the culture process, the viable cell number and lactic acid and acetic acid contents were measured, while non-targeted metabonomics was used to detect the differential metabolites and metabolic pathways. The results showed that soybean protein and soybean peptides promoted the growth and metabolism of Bifidobacterium animalis subsp. animalis JCM 1190, while digested soybean peptides had a better effect. Digested soybean peptides increased the viable cell number and lactic acid and acetic acid contents in the monoculture by regulating glycine, serine, and threonine metabolism, as well as pyruvate metabolism, the TCA cycle, glycolipid metabolism, and other metabolic pathways, balanced the ability of Bifidobacterium animalis subsp. animalis JCM 1190 and Escherichia coli JCM 1649 to utilize nitrogen sources during the early period and enhanced the competitiveness of Bifidobacterium animalis subsp. animalis JCM 1190 during the later period in co-culture.

Effects of multi-species probiotic supplementation on alcohol metabolism in rats.

Probiotics are known to protect against liver damage induced by the alcohol and acetaldehyde accumulation associated with alcohol intake. However, there have been few studies of the direct effect of probiotics on alcohol metabolism, and the types of probiotics that were previously analyzed were few in number. Here, we investigated the effects of 19 probiotic species on alcohol and acetaldehyde metabolism. Four probiotic species that had a relatively high tolerance to alcohol and metabolized alcohol and acetaldehyde effectively were identified: Lactobacillus gasseri CBT LGA1, Lactobacillus casei CBT LC5, Bifidobacterium lactis CBT BL3, and Bifidobacterium breve CBT BR3. These species also demonstrated high mRNA expression of alcohol and acetaldehyde dehydrogenases. ProAP4, a mixture of these four probiotics species and excipient, was then administered to rats for 2 weeks in advance of acute alcohol administration. The serum alcohol and acetaldehyde concentrations were significantly lower in the ProAP4-administered group than in the control and excipient groups. Thus, the administration of ProAP4, containing four probiotic species, quickly lowers blood alcohol and acetaldehyde concentrations in an alcohol and acetaldehyde dehydrogenasedependent manner. Furthermore, the serum alanine aminotransferase activity, which is indicative of liver damage, was significantly lower in the ProAP4 group than in the control group. The present findings suggest that ProAP4 may be an effective means of limiting alcohol-induced liver damage.

Safety and Efficacy of Probiotic Supplementation in Reducing the Incidence of Infections and Modulating Inflammation in the Elderly with Feeding Tubes: A Pilot, Double-Blind, Placebo-Controlled Study, "IntegPRO".

A double-blind, placebo-controlled study was performed in a sample of geriatric patients treated with home enteral nutrition (HEN) to analyze the efficacy of a probiotic supplement Proxian®, which contains Lactiplantibacillus plantarum LP01 (LMG P-21021), Lentilactobacillus buchneri Lb26 (DSM 16341), Bifidobacterium animalis subsp. lactis BS01 (LMG P-21384), and is enriched with zinc (Zn) and selenium (Se), in reducing the incidence of infections and modulating inflammation. Thirty-two subjects were enrolled (mean age 79.7 ± 10.3 years), 16 in the intervention group, 16 controls. They received Proxian® or placebo for 60 days. Patients were assessed at baseline (t0) and 60 (t1) and 90 (t2) days after the beginning. Infections were detected by information regarding their clinical manifestations and the incidence of antibiotic therapy. Levels of C-reactive protein (CRP) were measured to study inflammation. Information on bowel function, nutritional status and testimonials regarding the feasibility of administration of the product were collected. Differences between the two groups in number of infections (25% intervention group vs. 44% controls), antibiotic therapies (12% vs. 37%) and modulation of CRP levels (median CRP moved from 0.95 mg/L (t0), to 0.6 (t1) and 0.7 (t2) in intervention group vs. 0.7 mg/L, 0.5 and 0.7 in controls) did not reach statistical significance. No significant changes in bowel function and nutritional status were found. Caregivers' adherence was 100%. Results of this "IntegPRO" study showed that Proxian® is potentially safe, easy to administer and promising for further studies but it appears not to change the incidence of infections or modulate inflammation in elderly treated with HEN. The utility of Proxian® in reducing the incidence of infections and modulating inflammation in these subjects needs to be investigated by a larger multi-center clinical trial, and by using additional analyses on inflammatory markers and markers of infections.