Increased circulating butyrate and ursodeoxycholate during probiotic intervention in humans with type 2 diabetes

Background An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation (‘WBF-011’) in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. Results Here we report targeted and untargeted metabolomic measurements on fasting plasma (n = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation’s C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. Conclusion To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies.

A Rapid Screening Method of Candidate Probiotics for Inflammatory Bowel Diseases and the Anti-inflammatory Effect of the Selected Strain Bacillus smithii XY1

Inflammatory bowel disease (IBD) is a chronic intestinal disease associated with the inflammatory gastrointestinal tract and microbiome dysbiosis. Probiotics are a promising intervention, and several probiotics have been reported to positively affect IBD remission and prevention, particularly on ulcerative colitis (UC). However, there is still a limitation in the knowledge of effectiveness and safety of probiotics therapies for IBD. Exploring more potential probiotics helps to find extensive evidence for probiotic intervention. This study established a rapid method for probiotics candidate screening and finally screened out one strain with the best protective effect. Forty strains isolated from four different sources were used for this screening. Hemolysis tests and acute toxic test evaluated strain safety. Zebrafish were first treated with dextran sodium sulfate (DSS) for colitis induction, and every bacteria were individually added to the fish water subsequently. Results showed eight strains could lower the larvae mortality within 3 days under a 0.6% DSS concentration, including Lacticaseibacillus rhamnosus GG, L. rhamnosus NBRC3425, Bacillus smithii DSM4216, B. smithii XY1, Bacillus coagulans NBRC12583, Bacillus coagulans XY2, Lactobacillus parafarraginis XYRR2, and Bacillus licheniformis XYT3. Among eight, B. smithii XY1 was the only strain having the equal ability to alleviate neutrophil infiltration in the larvae intestine with that ability of prednisolone under a 0.5% DSS concentration. Bacillus smithii XY1 restored intestinal epithelial cell integrity after DSS damage, as well as regulated the gene expression inflammation-related factors, indicating its bio-function of inflammatory response alleviation.

Probiotics in Counteracting the Role of Neutrophils in Cancer Metastasis

Neutrophils are known for their role geared towards pathogen clearance by different mechanisms that they initiate, primarily by the release of neutrophil extracellular traps (NETs). However, their immune-surveillance capacity accompanied with plasticity in existing as interchangeable subsets, discovered recently, has revealed their property to contribute to complex cancer pathologies including tumor initiation, growth, angiogenesis and metastasis. Although there is a growing body of evidence suggesting a critical balance between the protumoral and antitumoral neutrophil phenotypes, an in-depth signaling pathway analysis would aid in determination of anticipatory, diagnostic and therapeutic targets. This review presents a comprehensive overview of the potential pathways involved in neutrophil-triggered cancer metastasis and introduces the influence of the microbial load and avenues for probiotic intervention.

Gut Microbiota in Canine Idiopathic Epilepsy: Effects of Disease and Treatment

Epilepsy is one of the most common neurological disorders in humans and dogs. The structure and composition of gut microbiome associated to this disorder has not yet been analyzed in depth but there is evidence that suggests a possible influence of gut bacteria in controlling seizures. The aim of this study was to investigate the changes in gut microbiota associated to canine idiopathic epilepsy (IE) and the possible influence of antiepileptic drugs (AEDs) on the modulation of this microbiota. Faecal microbiota composition was analyzed using sequencing of bacterial 16S rRNA gene in a group of healthy controls (n = 12) and a group of epileptic dogs both before (n = 10) and after a 30-day single treatment with phenobarbital or imepitoin (n = 9). Epileptic dogs showed significantly reduced abundance of GABA (Pseudomonadales, Pseudomonadaceae, Pseudomonas and Pseudomona_graminis) and SCFAs-producing bacteria (Peptococcaceae, Ruminococcaceae and Anaerotruncus) as well as bacteria associated with reduced risk for brain disease (Prevotellaceae) than control dogs. The administration of AEDs during 30 days did not modify the gut microbiota composition. These results are expected to contribute to the understanding of canine idiopathic epilepsy and open up the possibility of studying new therapeutic approaches for this disorder, including probiotic intervention to restore gut microbiota in epileptic individuals.

Lactobacillus rhamnosus Probio-M9 Improves the Quality of Life in Stressed Adults by Gut Microbiota

To evaluate the effect of the probiotic, Lactobacillus rhamnosus Probio-M9 (Probio-M9), on the quality of life in stressed adults. Methods: Twelve postgraduate student volunteers were recruited. Six volunteers received oral Probio-M9 for 21 days, while the remaining six received a placebo instead. Fecal samples were collected from the volunteers before and after the intervention. Metagenomic sequencing, nontargeted metabonomics, and quality-of-life follow-up questionnaires were used to evaluate the impact of Probio-M9 consumption on the gut microbiota and life quality of the volunteers. Results: Probio-M9 improved the psychological and physiological quality-of-life symptoms significantly in stressed adults (p < 0.05). The probiotic intervention was beneficial in increasing and maintaining the diversity of gut microbiota. The abundance of Barnesiella and Akkermansia increased in the probiotics group. The feature metabolites of pyridoxamine, dopamine, and 5-hydroxytryptamine (5-HT) were positively correlated with Barnesiella and Akkermansia levels, which might be why the mental state of the volunteers in the probiotic group improved after taking Probio-M9. Conclusions: We identified that oral Probio-M9 can regulate the stability of gut microbiota and affect the related beneficial metabolites, thereby affecting the quality of life (QoL) of stressed adults. Probio-M9 might improve the psychological and physiological quality of life in stressed adults via the gut-brain axis pathway. The causal relationship should be further explored in future studies.

Probiotic Interventions Alleviate Food Allergy Symptoms Correlated With Cesarean Section: A Murine Model

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.

Probiotics maintain the gut microbiome homeostasis during Indian Antarctic expedition by ship

Ship voyage to Antarctica is a stressful journey for expedition members. The response of human gut microbiota to ship voyage and a feasible approach to maintain gut health, is still unexplored. The present findings describe a 24-day long longitudinal study involving 19 members from 38th Indian Antarctic Expedition, to investigate the impact of ship voyage and effect of probiotic intervention on gut microbiota. Fecal samples collected on day 0 as baseline and at the end of ship voyage (day 24), were analyzed using whole genome shotgun sequencing. Probiotic intervention reduced the sea sickness by 10% compared to 44% in placebo group. The gut microbiome in placebo group members on day 0 and day 24, indicated significant alteration compared to a marginal change in the microbial composition in probiotic group. Functional analysis revealed significant alterations in carbohydrate and amino acid metabolism. Carbohydrate-active enzymes analysis represented functional genes involved in glycoside hydrolases, glycosyltransferases and carbohydrate binding modules, for maintaining gut microbiome homeostasis. Suggesting thereby the possible mechanism of probiotic in stabilizing and restoring gut microflora during stressful ship journey. The present study is first of its kind, providing a feasible approach for protecting gut health during Antarctic expedition involving ship voyage.