Probiotic Bifidobacterium Longum Research Articles

Metabolome-associated psychological comorbidities improvement in irritable bowel syndrome patients receiving a probiotic

Our recent randomized, placebo-controlled study in Irritable Bowel Syndrome (IBS) patients with diarrhea or alternating bowel habits showed that the probiotic Bifidobacterium longum (BL) NCC3001 improves depression scores and decreases brain emotional reactivity. However, the involved metabolic pathways remain unclear. This analysis aimed to investigate the biochemical pathways underlying the beneficial effects of BL NCC3001 using metabolomic profiling. Patients received probiotic (1x 1010CFU, n=16) or placebo (n=19) daily for 6 weeks. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Brain activity in response to negative emotional stimuli was assessed by functional Magnetic Resonance Imaging. Probiotic fecal abundance was quantified by qPCR. Quantitative measurement of specific panels of plasma host-microbial metabolites was performed by mass spectrometry-based metabolomics. Probiotic abundance in feces was associated with improvements in anxiety and depression scores, and a decrease in amygdala activation. The probiotic treatment increased the levels of butyric acid, tryptophan, N-acetyl tryptophan, glycine-conjugated bile acids, and free fatty acids. Butyric acid concentration correlated with lower anxiety and depression scores, and decreased amygdala activation. Furthermore, butyric acid concentration correlated with the probiotic abundance in feces. In patients with non-constipation IBS, improvements in psychological comorbidities and brain emotional reactivity were associated with an increased abundance of BL NCC3001 in feces and specific plasma metabolites, mainly butyric acid. These findings suggest the importance of a probiotic to thrive in the gut and highlight butyric acid as a potential biochemical marker linking microbial metabolism with beneficial effects on the gut-brain axis.

Selenium-enriched Bifidobacterium Longum DD98 significantly improves the efficacy of Mesalazine and Cyclosporin A in colitis mice

The incidence of ulcerative colitis (UC) is increasing worldwide and therapeutic drugs for UC are limited. Improvement of microbiome composition with the use of probiotics has the potential to increase the therapeutic index of UC drugs. Several lines of evidence suggested that Bifidobacterium significantly improve colitis by restoring the altered gut microbiota in DSS-treated mice, however the adjuvant effect of Bifidobacterium with UC drugs remains unknown. In this study, we tested the adjuvant potential of probiotic selenium-enriched Bifidobacterium Longum DD98 (SeDD98) on Mesalazine and Cyclosporin A (CsA) two medications used in the treatment of UC. We found that SeDD98 significantly improved the efficacy of Mesalazine and CsA in UC. The combination of SeDD98 and CsA showed the strongest efficacy in decreasing colitis histological scores, inflammation, and oxidative stress. Next we demonstrated that the combination of SeDD98 and CsA shifted the gut microbiota composition and increased with higher alpha diversity as well as beneficial bacteria such as Ruminococcaceae_UCG-014 and Lachnospiraceae_NK4A136. In parallel, we assessed if the adjuvant of SeDD98 with CsA had an impact on CsA-induced kidney injury which represents one of the major side effects. We found that SeDD98 significantly improved CsA nephrotoxicity in UC mice. We then validated this observation using chronic kidney disease (CKD) mice induced by CsA administration. These results demonstrated that SeDD98 in combination with CsA was associated with increased efficacy and reduced nephrotoxicity altogether, providing the scientific basis for the adjuvant therapy of probiotics in UC.

The Effect of Probiotics on Radiation Enteritis in Endometrial Cancer Patients Undergoing Radiotherapy

Introduction: Radiation enteritis is damage to the small and large intestines caused by radiation therapy for regional cancer treatment. The incidence is around 90% in patients undergoing radiation in the pelvic and abdominal regions. This study aimed to report the effect of probiotics on radiation enteritis in endometrial cancer patients. Case presentation: A 57-year-old morbidly obese woman diagnosed with endometrial cancer underwent chemoradiation therapy. On the 21st out of 25 radiation sessions and the 2nd chemotherapy session, the patient visited the nutrition clinic at the Radiation Oncology Therapy Center with a complaint of diarrhea for the past 5 days. The diarrhea occurred approximately 10 times a day, with each bowel movement being approximately 50 ml and yellow in color. The patient was then treated with anti-diarrheal therapy, probiotics (Lactobacillus acidophilus, Bifidobacterium longum, and Streptococcus thermophilus) 2 times a day, zinc 20 mg once a day, and prescribed a low-fat and lactose-free diet. After monitoring on the 21st day, the frequency of liquid bowel movements decreased to 2 times a day, and the appetite improved. Conclusion: Patients with radiation enteritis who are given probiotics may experience a reduction in symptoms of acute diarrhea. Direct administration of probiotics increases beneficial bacteria in the digestive tract.

P135 Mixed probiotics containing Bifidobacterium longum and its metabolites inhibit the formation of NLRP3 inflammasomes by suppressing GBP5 expression in macrophages in ulcerative colitis

Abstract Background Ulcerative Colitis (UC) is a non-specific chronic inflammation of the intestine. As an intestinal disease with a gradually increasing incidence in recent years and increasingly valued by medical staff, UC has a close relationship with intestinal flora. At present, domestic and foreign guidelines point out that probiotics can be used to induce remission in ulcerative colitis, but there are no clear instructions on the selection of probiotics, the use of dosage forms, and the dosage of probiotics, and there is a lack of relevant clinical and basic research. This study aims to explore the distinct therapeutic effects of mixed probiotics and individual strains of probiotics (Bifidobacterium longum), as well as elucidate the underlying mechanisms responsible for these variations. Methods A total of 90 patients with ulcerative colitis (UC) were enrolled in our center, who were subsequently divided into three groups: control group, single strain probiotic group (Bifidobacterium longum), and mixed probiotic group. After three months of adjuvant probiotic therapy, serum and fecal samples were collected for comparative analysis of therapeutic effects using ELISA and fecal 16s rDNA and metabolome sequence analysis. Mixed probiotic and Bifidobacterium longum were cultured in BHIs in an anaerobic chamber. The supernatant obtained after bacterial cultivation was subjected to metabolome sequence analysis. Human colonic organoids and Caco-2 cells were co-cultured with mixed probiotic and Bifidobacterium longum subsequent to inflammation induction, and cytotoxicity, permeability, and inflammatory cytokine release were assessed. THP1 cells were also to co-cultured with mixed probiotic and Bifidobacterium longum, and expression of virulence genes was analyzed using RT-qPCR, transcriptome sequencing, and western blot. GBP5 gene manipulated cell and mouse model were used to evaluate inflammation and apoptosis. Results The utilization of mixed probiotic therapy in patients with UC demonstrated significantly superior therapeutic efficacy compared to those receiving a single strain probiotic (Bifidobacterium longum). Differential metabolite 8-Deoxylactucinwas identified among various groups through the metabolome sequence analysis of clinical patients’ feces, bacterial culture supernatant, and mouse feces. Through in vitro and in vivo experiments, it has been demonstrated that 8-Deoxylactucin exhibits inhibitory effects on the expression of GBP5 in THP-1 cells and ameliorates inflammation. Conclusion Collectively, these findings indicate that mixed probiotics and its metabolites suppress GBP5 expression in macrophages in ulcerative colitis.

Bifidobacterium longum SX-1326 ameliorates gastrointestinal toxicity after irinotecan chemotherapy via modulating the P53 signaling pathway and brain-gut axis

BackgroundColorectal cancer (CRC) is a prevalent malignant malignancy affecting the gastrointestinal tract that is usually treated clinically with chemotherapeutic agents, whereas chemotherapeutic agents can cause severe gastrointestinal toxicity, which brings great pain to patients. Therefore, finding effective adjuvant agents for chemotherapy is crucial.MethodsIn this study, a CRC mouse model was successfully constructed using AOM/DSS, and the treatment was carried out by probiotic Bifidobacterium longum SX-1326 (B. longum SX-1326) in combination with irinotecan. Combining with various techniques of modern biomedical research, such as Hematoxylin and Eosin (H&E), Immunohistochemistry (IHC), Western blotting and 16S rDNA sequencing, we intend to elucidate the effect and mechanism of B. longum SX-1326 in improving the anticancer efficacy and reducing the side effects on the different levels of molecules, animals, and bacteria.ResultsOur results showed that B. longum SX-1326 enhanced the expression of Cleaved Caspase-3 (M vs. U = p < 0.01) and down-regulated the expression level of B-cell lymphoma-2 (Bcl-2) through up-regulation of the p53 signaling pathway in CRC mice, which resulted in an adjuvant effect on the treatment of CRC with irinotecan. Moreover, B. longum SX-1326 was also able to regulate the gut-brain-axis (GBA) by restoring damaged enterochromaffin cells, reducing the release of 5-hydroxytryptamine (5-HT) in brain tissue (I vs. U = 89.26 vs. 75.03, p < 0.05), and further alleviating the adverse effects of nausea and vomiting. In addition, B. longum SX-1326 reversed dysbiosis in CRC model mice by increasing the levels of Dehalobacterium, Ruminnococcus, and Mucispirillum. And further alleviated colorectal inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway.ConclusionsIn conclusion, our work reveals that B. longum SX-1326 has a favorable effect in adjuvant irinotecan for CRC and amelioration of post-chemotherapy side effects, and also provides the theoretical basis and data for finding a safe and efficient chemotherapeutic adjuvant.

Биотехнология производства мягких сыров из смеси коровьего и козьего молока с функциональными ингредиентами

The aim of this research is to develop a biotechnology of soft cheeses with func-tional ingredients based on a mixture of cow’s and goat’s milk taken in a ratio of 60:40, subjected to acoustic cavitation at 75 kHz and an exposure time of 17 min. To achieve the research aim, the tasks of selecting and determining the number of functional ingredients, determining the technological parameters of the production of soft cheeses with their use were solved. As a result, the biotechnology of two types of soft cheeses «Dieticheskij» and «Funkcionalnyj» has been developed. In the biotechnology of soft cheese «Dieticheskij», a complex preparation «Bivestin-lacto» containing cultures of probiotics Bifidobacterium longum MS-42, Lactoba-cillus plantarum 8PA-3 and dietary fiber «Citri-Fi» of medium grinding was used as a functional ingredient. Soft cheese «Funkcionalnyj» is enriched with a biocomponent containing probiotic cultures of Lactobacillus acidophilus La-5, Lactobacillus delbrueckii subsp. Bulgaricus, Bifidobacterium lactis, Streptococcus thermophilus, as well as «Selexen» – a source of selenium, «Curcumin» in micellar form and dietary fiber «Citri-Fi». Their organoleptic, chemical, microbiological parameters, as well as nutritional, energy value and shelf life have been determined.

Growth and metabolic behavior of probiotic Bifidobacterium longum subsp. longum in minimally supplemented soy (tofu) whey

Soy (tofu) whey is a liquid side-stream from tofu production. It is a nutrient-rich substrate that can be converted into beverages by fermentation. In this study, soy whey media supplemented with various nutrients (control, glucose, glucose + cysteine-HCl (GC), glucose + cysteine-HCl + yeast extract (GCY)) were evaluated as fermentation substrates for probiotic Bifidobacterium longum subsp. longum BB536. GC and GCY facilitated strain BB536 growth leading to the production of acetic and lactic acid. However, there was no significant decrease in sugar content after fermentation, while succinic acid and selected amino acids such as cysteine showed significant decreases after fermentation. Vitamin B12 (2.12 µg/L) was found only in fermented GCY samples. Endogenous volatile compounds such as heptanal and hexenal in tofu whey were reduced to low or trace levels while short-chain fatty acids, 2,3-butanedione and volatile sulfur compounds such as hydrogen sulfide and 3-methylthiophene were produced. Iron and potassium contents in the fermented soy whey increased after fermentation. This research provides further insights into the possibility of utilizing B. longum BB536 to ferment soy whey into a novel functional beverage or ingredient.

Alternative Fermented Soy-Based Beverage: Impact of Inulin on the Growth of Probiotic Strains and Starter Culture

The number of people with dietary restrictions on dairy products has increased significantly due to lactose intolerance/allergy or adoption of vegan diets. Organic acid-producing probiotics have been used in fermented beverages, such as those based on soy, with good results. Such molecules have in fact been described for their role in sensory analyses and benefits to human health. Therefore, this study suggested the evaluation of an alternative soy extract-based beverage that could act as a functional food. For this purpose, products and biomass concentrations were monitored throughout soy extract fermentation through acidification kinetics and cell count. The effect of inulin on the growth of the probiotic strains Bifidobacterium longum and Lactobacillus acidophilus in co-culture with Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus was evaluated (technical replicates). It was observed that the addition of inulin reduced the time of fermentation by L. acidophilus, while no statistically significant effect was observed in the post-acidification period. In B. longum fermentation, the process did not change in the presence of inulin, but there was a significant increase in viability and survival in the post-acidification period. Therefore, it can be concluded that the strains studied can be used in the formulation of soy-based drinks and that inulin positively influenced the viability of both probiotics in fermented drinks tested.

Elucidation of the Tissue Distribution and Host Immunostimulatory Activity of Exogenously Administered Probiotic-Derived Extracellular Vesicles for Immunoadjuvant.

Extracellular vesicles (EVs) are cell-derived nanoparticles that can be used as novel biomaterials. In the development of EVs-based therapeutic systems, it is essential to understand the in vivo fate of exogenously administered EVs and subsequent biological responses mediated by EVs. Although probiotics and microorganisms that modulate the host immune system also secrete EVs, their tissue distribution and biological reactions after administration to the host have not been sufficiently elucidated. In this study, we characterized EVs released from the probiotics Bifidobacterium longum (B-EVs) and Lactobacillus plantarum WCFS1 (L-EVs) in terms of tissue distribution and immune-activating capacity after intravenous and subcutaneous administration in mice. B-EVs and L-EVs exhibited particle sizes of approximately 100-160 nm and negative zeta potentials. These EVs contained peptidoglycan, DNA, and RNA as their cargoes. Intravenously administered B-EVs and L-EVs mainly accumulated in the liver and spleen. Furthermore, liver F4/80 and splenic CD169 macrophages took up the intravenously administered EVs. Subcutaneously administered B-EVs and L-EVs accumulated in the lymph nodes and were mainly located in the B-lymphocyte zone, indicating that exogenously administered probiotic-derived EVs showed a similar biodistribution, irrespective of the EVs-secreting cell type. Evaluation of EVs-mediated immune reactions demonstrated that intravenously administered EVs showed little activation potency. In contrast, subcutaneously administered B-EVs strongly increased the expression of inflammatory cytokine (TNF-α) and co-stimulatory molecules (CD40 and CD80) than L-EVs. These findings indicate that the subcutaneous administration of B-EVs is a useful strategy for the development of novel EVs-based immunotherapies.

Modulation of microbiota as a target in the management of patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common diseases of the digestive tract. IBS negatively affects the quality of life and work ability of patients. It is generally accepted that IBS is an important medical and social problem associated with high financial costs both on the part of the patient and the public health system. The pathophysiology of the disease involves the participation of many factors (genetic, dietary, psychosocial, infectious) and the mechanisms of their implementation, including disruption of interaction along the functional “gut-brain axis”, visceral hypersensitivity, changes in motility, low-grade inflammation, increased permeability of the epithelial intestinal barrier, modulation of microbiota, changes in neurohumoral regulation and processes of central processing of peripheral stimuli. Research shows an important role for gut microbiota in the development of IBS. Modulation of the intestinal microbiota through diet, the use of pre- and probiotics or fecal microbiota transplantation is considered as a promising target for disease therapy. A reduction in the number of bacteria of the genus Bifidobacterium is described as a universal change in the microbiota in IBS, regardless of the clinical course and severity of the disease and the possibility of using different strains of Bifidobacterium in treatment regimens for the disease is of particular interest. This article provides a review of the literature on modern approaches to prescribing probiotics for IBS. Using our own clinical observations as an example, we demonstrated the effectiveness and safety of prolonged administration of the probiotic strain Bifidobacterium longum 35624® for up to 12 weeks.

Ameliorating Effects of Bifidobacterium longum subsp. infantis FB3-14 against High-Fat-Diet-Induced Obesity and Gut Microbiota Disorder.

Obesity has emerged as one of the most prevalent chronic diseases worldwide. Our study was conducted to investigate the anti-obese potential of novel probiotic Bifidobacterium longum subsp. infantis FB3-14 (FB3-14) and the underlying molecular mechanisms in high-fat diet (HFD)-fed mice. The results demonstrated that an 8-week FB3-14 intervention significantly suppressed the HFD-induced body and fat weight gain and abnormal alterations of the serum lipid parameter, restoring the levels of cholesterol (4.29 mmol/L) and low-density lipoprotein cholesterol (3.42 mmol/L). FB3-14 treatment also attenuated adipocyte expansion, hepatic injury, and low-grade systemic inflammation and restored the expressions of lipid-metabolism-related genes, including Hsl, Leptin, and Adiponectin. Furthermore, FB3-14 was observed to reduce the Firmicutes/Bacteroidetes ratio in obese mice; increase the abundance of Akkermansia muciniphila, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and Bifidobacterim; and upregulate G protein-coupled receptor41 associated with higher levels of butyric acid. These results indicate the protective effectiveness of FB3-14 in HFD-driven obesity and gut microbiota disorders, highlighting the promising potential of FB3-14 as a functional nutrition supplement.

An 8-Week Course of Bifidobacterium longum 35624® Is Associated with a Reduction in the Symptoms of Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is one of the disorders most frequently diagnosed by gastroenterologists. Probiotics are promising tools for the management of IBS. The objective of the present study was to evaluate the effectiveness and tolerability of a probiotic (Bifidobacterium longum 35624®) in adults (aged 18 or over) with IBS (as defined by the Rome IV criteria). In an open-label, observational, post-market study conducted in Germany, adults with IBS and a prior recommendation for the intake of B. longum 35624® were recruited by family physicians. During the 8-week course of treatment, the study participants filled out a weekly questionnaire that enabled calculation of a total IBS symptom score (TISS, the sum of abdominal pain, bloating, passage of gas, constipation, and diarrhea individual symptom scores) and the well-known IBS severity scoring system (IBS-SSS) score. Thirty-seven patients were included. The course of B. longum 35624® was associated with a significant reduction (43.4%) in the TISS vs. baseline. The mean individual symptom grades for passage of gas and bloating fell significantly from "moderate" at baseline to "very mild to mild" after 8 weeks of treatment, whereas those for abdominal pain and diarrhea fell significantly from "mild to moderate" to "very mild to mild." Over 60% of the participants achieved clinically meaningful reductions in the TISS (> 30%) and the IBS-SSS score (> 50 points). The effectiveness of B. longum 35624® was rated as "good to satisfactory" by study participants and the investigating physicians. One mild adverse event (nausea) was potentially linked to the study treatment. We conclude that an 8-week course of B. longum 35624® was associated with significant, clinically meaningful symptom relief in a typical population of adult patients with IBS.

Probiotics improve polystyrene microplastics-induced male reproductive toxicity in mice by alleviating inflammatory response

As a new type of environmental pollutant, microplastics have been garnered increasing attention, especially in regard to their effects on the reproductive system. However, researchers have yet to report whether prevention and treatment measures exist for reproductive injury caused by microplastics. The aim of this study was therefore to explore the mechanism of spermatogenic injury induced by polystyrene microplastics (PS-MPs) and the intervention effect of probiotics based on the gut microbiota-testis axis. Mice were orally exposed for 35 days to 5 µm of PS-MPs with a gavage dose was 0.1 mg/day, and the intervention group was given probiotics (Lactobacillus, Bifidobacterium longum, and Enterococcus) orally. Fecal samples were then subjected to 16 S rRNA sequencing analysis, and sperm motion was analyzed by a Hamilton-Thorne Sperm analyzer. The results showed that PS-MPs exposed mice had significant spermatogenic dysfunction and testicular inflammation. In addition, the intestinal microbial structure of exposed mice changed significantly; the abundance of Lactobacillus decreased, and the abundance of Prevotella increased. Furthermore, with fecal microbiota transplantation, the recipient mice showed a significant decrease in sperm quality. However, probiotics supplementation helped inhibit the activation of IL-17A signaling driven by gut microbes, thereby alleviating the inflammatory response and improving sperm quality decline caused by PS-MPs. These results may provide a scientific basis for further understanding of the mechanism of male reproductive damage caused by environmental pollutants such as microplastics and for novel reproductive damage intervention measures.

The Effect of Human Milk Oligosaccharides and Bifidobacterium longum subspecies infantis Bi-26 on Simulated Infant Gut Microbiome and Metabolites.

Human milk oligosaccharides (HMOs) shape the developing infant gut microbiota. In this study, a semi-continuous colon simulator was used to evaluate the effect of 2 HMOs-2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL)-on the composition of infant faecal microbiota and microbial metabolites. The simulations were performed with and without a probiotic Bifidobacterium longum subspecies infantis Bi-26 (Bi-26) and compared with a control that lacked an additional carbon source. The treatments with HMOs decreased α-diversity and increased Bifidobacterium species versus the control, but the Bifidobacterium species differed between simulations. The levels of acetic acid and the sum of all short-chain fatty acids (SCFAs) trended toward an increase with 2'-FL, as did lactic acid with 2'-FL and 3-FL, compared with control. A clear correlation was seen between the consumption of HMOs and the increase in SCFAs (-0.72) and SCFAs + lactic acid (-0.77), whereas the correlation between HMO consumption and higher total bifidobacterial numbers was moderate (-0.46). Bi-26 decreased propionic acid levels with 2'-FL. In conclusion, whereas infant faecal microbiota varied between infant donors, the addition of 2'-FL and 3-FL, alone or in combination, increased the relative abundance and numbers Bifidobacterium species in the semi-continuous colon simulation model, correlating with the production of microbial metabolites. These findings may suggest that HMOs and probiotics benefit the developing infant gut microbiota.

Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs.

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)-sialylactose (3'SL)-on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3'SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3'SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3'SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence.

Entrapment of probiotic (Bifidobacterium longum) in bilayer emulsion film with enhanced barrier property for improving viability

The gelatin/gellan gum based-bilayer emulsion film was developed in this work to improve the survivability of Bifidobacterium longum during the storage process. The baobab seed oil (BO) was added to the gelatin (GE) matrix to develop emulsion film as the barrier outer layer. The blueberry anthocyanin extract (BE) was incorporated into the gellan gum (GG)-based inner layer to enhance the viability of B. longum. The SEM and FTIR results revealed that the probiotics were successfully entrapped in BO/BE-loaded bilayer film. The greatest survivability and viable cell numbers of the B. longum during the storage period were observed in the BO/BE loaded bilayer film. Furthermore, the stability of the colorful patterns by electrochemical writing was also evaluated in this work. Finally, the GE/BO-GG/BE/BM maintain satisfactory probiotic viability in steamed bread coating application. Hence, the GE/BO-GG/BE/BM bilayer film could be considered a novel material to deliver and protect the probiotics in food applications.

Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium-Pilocarpine Model of Temporal Lobe Epilepsy in Rats.

Epilepsy is a challenging brain disorder that is often difficult to treat with conventional therapies. The gut microbiota has been shown to play an important role in the development of neuropsychiatric disorders, including epilepsy. In this study, the effects of Bifidobacterium longum, a probiotic, on inflammation, neuronal degeneration, and behavior are evaluated in a lithium-pilocarpine model of temporal lobe epilepsy (TLE) induced in young adult rats. B. longum was administered orally at a dose of 109 CFU/rat for 30 days after pilocarpine injection. The results show that B. longum treatment has beneficial effects on the TLE-induced changes in anxiety levels, neuronal death in the amygdala, and body weight recovery. In addition, B. longum increased the expression of anti-inflammatory and neuroprotective genes, such as Il1rn and Pparg. However, the probiotic had little effect on TLE-induced astrogliosis and microgliosis and did not reduce neuronal death in the hippocampus and temporal cortex. The study suggests that B. longum may have a beneficial effect on TLE and may provide valuable insights into the role of gut bacteria in epileptogenesis. In addition, the results show that B. longum may be a promising drug for the comprehensive treatment of epilepsy.

Multi-omics reveals Bifidobacterium longum CECT7894 alleviate food allergy by regulating the Sphingolipid metabolism pathway

Food allergy (FA) is one of the global human health problems, affecting about 1 in 12 children and 1 in 10 adults worldwide. Probiotics have alleviating effects on FA, but the mechanisms have not been fully understood. We sought to explore the therapeutic potential of probiotics Bifidobacterium longum CECT7894 (B. longum CECT7894) on anaphylaxis in the ovalbumin (OVA)-induced FA model using an integrated multiomics approaches. The results revealed treatment with B. longum CECT7894 relieved OVA-induced allergic symptoms such as pathological changes in small intestine to some extent. Furthermore, probiotics utilization also reduced IgE levels. The transcriptomic data demonstrated that the expressions of genes associated with sphingolipid metabolism were altered in the group received B. longum CECT7894 compared to the sensitized group, including Sgpl1, Trpc1 and Prss8. In addition, the abundances of Sphingobacterium at the genus level, Sphingobacterium sp. 21 and B. longum at the species level, which might related with sphingolipid metabolism, were significantly altered by B. longum CECT7894 when compared to the OVA group. Employed the metabolomics analysis, phytosphingosine, C16 sphinganine, sphinganine and sphingosine were identified as significantly changed metabolites and sphingolipid metabolism pathway was significantly enriched by pathway enrichment analysis. The Spearman's correlation analysis further demonstrated that there were strong correlations between serum biochemical indicators, transcripts, gut microbiota and metabolites. Based on the findings described above, from the perspective of genes, gut flora and metabolites changes, it can be concluded that B. longum CECT7894 might suppress OVA-induced FA by regulating the sphingolipid metabolism pathway.

A Probiotic Intervention With Bifidobacterium longum NCC3001 on Perinatal Mood Outcomes (PROMOTE Study): Protocol for a Decentralized Randomized Controlled Trial

Perinatal mood disorders such as depression and anxiety are common, with subclinical symptomology manifesting as perinatal mood disturbances being even more prevalent. These could potentially affect breastfeeding practices and infant development. Pregnant and lactating women usually limit their exposure to medications, including those for psychological symptoms. Interestingly, the naturally occurring probiotic Bifidobacterium longum (BL) NCC3001 has been shown to reduce anxious behavior in preclinical models and feelings of low mood in nonpregnant human adults. During the COVID-19 pandemic, mental health issues increased, and conventionally conducted clinical trials were restricted by social distancing regulations. This study, Probiotics on Mothers' Mood and Stress (PROMOTE), aimed to use a decentralized clinical trial design to test whether BL NCC3001 can reduce symptoms of depression, anxiety, and stress over the perinatal period. This double-blind, placebo-controlled, randomized, and 3-parallel-arm study aimed to recruit 180 women to evaluate the efficacy of the probiotic taken either during pregnancy and post partum (from 28-32 weeks' gestation until 12 weeks after delivery; n=60, 33.3%) or post partum only (from birth until 12 weeks after delivery; n=60, 33.3%) in comparison with a placebo control group (n=60, 33.3%). Participants consumed the probiotic or matched placebo in a drink once daily. Mood outcomes were measured using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale questionnaires, captured electronically at baseline (28-32 weeks' gestation) and during e-study sessions over 5 further time points (36 weeks' gestation; 9 days post partum; and 4, 8, and 12 weeks post partum). Saliva and stool samples were collected longitudinally at home to provide mechanistic insights. In total, 520 women registered their interest on our website, of whom 184 (35.4%) were eligible and randomized. Of these 184 participants, 5 (2.7%) withdrew after randomization, leaving 179 (97.3%) who completed the study. Recruitment occurred between November 7, 2020, and August 20, 2021. Advertising on social media brought in 46.9% (244/520) of the prospective participants, followed by parenting-specific websites (116/520, 22.3%). Nationwide recruitment was achieved. Data processing is ongoing, and there are no outcomes to report yet. Multiple converging factors contributed to speedy recruitment and retention of participants despite COVID-19-related restrictions. This decentralized trial design sets a precedent for similar studies, in addition to potentially providing novel evidence on the impact of BL NCC3001 on symptoms of perinatal mood disturbances. This study was ideal for remote conduct: because of the high digital literacy and public trust in digital security in Singapore, the intervention could be self-administered without regular clinical monitoring, and the eligibility criteria and outcomes were measured using electronic questionnaires and self-collected biological samples. This design was particularly suited for a group considered vulnerable-pregnant women-during the challenging times of COVID-19-related social restrictions. ClinicalTrials.gov NCT04685252; https://clinicaltrials.gov/ct2/show/NCT04685252. DERR1-10.2196/41751.

Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.