Showing papers by "Arthur C. Ouwehand published in 2021"

Viral Infections, the Microbiome, and Probiotics.

Abstract: Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.

Regulation of hBD-2, hBD-3, hCAP18/LL37, and Proinflammatory Cytokine Secretion by Human Milk Oligosaccharides in an Organotypic Oral Mucosal Model.

Abstract: Human milk oligosaccharides (HMOs), the third largest solid fraction in human milk, can modulate inflammation through Toll-like receptor signaling, but little is known about their immunomodulatory potential in the oral cavity. In this study, we determined whether the HMOs 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) regulate human-beta defensin (hBD)-2 and -3, cathelicidin (hCAP18/LL-37), and cytokine responses in human gingival cells using a three-dimensional oral mucosal culture model. The model was incubated with 0.1% or 1% 2'-FL and 3-FL, alone and in combination, for 5 or 24 h, and hBD-2, hBD-3, and hCAP18/LL-37 were analyzed by immunohistochemistry. The expression profiles of interleukin (IL)-1, IL-1RA, IL-8, and monocyte chemoattractant protein (MCP)-1 were determined by LUMINEX immunoassay. The combination of 1% 2'-FL and 1% 3-FL, and 1% 3-FL alone, for 24 h upregulated hBD-2 protein expression significantly (p < 0.001 and p = 0.016, respectively). No changes in the other antimicrobial peptides or proinflammatory cytokines were observed. Thus, 3-FL, alone and in combination with 2'-FL, stimulates oral mucosal secretion of hBD-2, without effecting a proinflammatory response when studied in an oral mucosal culture model.

Effects of Colonic Fermentation Products of Polydextrose, Lactitol and Xylitol on Intestinal Barrier Repair In Vitro

Abstract: Many functional food ingredients improve intestinal barrier function through their colonic fermentation products short chain fatty acids (SCFAs). Effects of individual SCFAs have been well studied, but the effects of SCFA mixtures–colonic fermentation products have been rarely investigated. Therefore, this study used an EnteroMix semi-continuous model to simulate the colonic fermentation of three widely used food ingredients, polydextrose, lactitol and xylitol in vitro, and investigated the effects of their fermentation products on impaired colonic epithelial barrier function through a mucus-secreting human HT29-MTX-E12 cell model. Fermentation of polydextrose and lactitol produced mainly acetate, while fermentation of xylitol produced mainly butyrate and resulted in a much higher butyrate proportion. All fermentation products significantly improved intestinal barrier repairing as measured by increased transepithelial electrical resistance and decreased paracellular permeability. Among these, xylitol fermentation products exhibited better repairing effects than that of polydextrose and lactitol. Correlation analysis showed that the repairing effects were attribute to butyrate but not acetate or propionate, implying that in the fermentation products butyrate may play a major role in improving intestinal barrier function. Our results suggest that functional food ingredients that mainly produce butyrate during fermentation may be of more value for improving gut health related to chronic diseases.

Transcriptomics reveal different metabolic strategies for acid resistance and gamma-aminobutyric acid (GABA) production in select Levilactobacillus brevis strains.

Abstract: Background Of the many neurotransmitters in humans, gamma-aminobutyric acid (GABA) shows potential for improving several mental health indications such as stress and anxiety. The microbiota-gut-brain axis is an important pathway for GABAergic effects, as microbially-secreted GABA within the gut can affect host mental health outcomes. Understanding the molecular characteristics of GABA production by microbes within the gut can offer insight to novel therapies for mental health. Results Three strains of Levilactobacillus brevis with syntenous glutamate decarboxylase (GAD) operons were evaluated for overall growth, glutamate utilization, and GABA production in typical synthetic growth media supplemented with monosodium glutamate (MSG). Levilactobacillus brevis Lbr-6108™ (Lbr-6108), formerly known as L. brevis DPC 6108, and Levilactobacillus brevis Lbr-35 ™ (Lbr-35) had similar growth profiles but differed significantly in GABA secretion and acid resistance. Lbr-6108 produced GABA early within the growth phase and produced significantly more GABA than Lbr-35 and the type strain Levilactobacillus brevis ATCC 14869 after the stationary phase. The global gene expression during GABA production at several timepoints was determined by RNA sequencing. The GAD operon, responsible for GABA production and secretion, activated in Lbr-6108 after only 6 h of fermentation and continued throughout the stationary phase. Furthermore, Lbr-6108 activated many different acid resistance mechanisms concurrently, which contribute to acid tolerance and energy production. In contrast, Lbr-35, which has a genetically similar GAD operon, including two copies of the GAD gene, showed no upregulation of the GAD operon, even when cultured with MSG. Conclusions This study is the first to evaluate whole transcriptome changes in Levilactobacillus brevis during GABA production in different growth phases. The concurrent expression of multiple acid-resistance mechanisms reveals niche-specific metabolic functionality between common human commensals and highlights the complex regulation of GABA metabolism in this important microbial species. Furthermore, the increased and rapid GABA production of Lbr-6108 highlights the strain's potential as a therapeutic and the overall value of screening microbes for effector molecule output.

Effects of Bifidobacterium animalis ssp. lactis 420 on gastrointestinal inflammation induced by a nonsteroidal anti-inflammatory drug: A randomized, placebo-controlled, double-blind clinical trial.

Abstract: AIMS Use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause damage to the gastric and duodenal mucosa. Some probiotics have proven useful in ameliorating the harmful side-effects of NSAIDs. Our aim was to evaluate whether oral administration of Bifidobacterium animalis ssp. lactis 420 (B420) can attenuate the increase of calprotectin excretion into faeces induced by intake of diclofenac sustained-release tablets. METHODS A double-blind, parallel-group, placebo-controlled and randomized clinical study was performed in 50 healthy male and female volunteers aged 20-40 years, in Finland. Study participation consisted of 4 phases: run-in, intervention with B420 or placebo, B420 or placebo + NSAID treatment, and follow-up. The primary outcome was the concentration of calprotectin in faeces. Secondary outcomes were haemoglobin and microbial DNA in faeces and blood haemoglobin levels. RESULTS Intake of diclofenac increased the faecal excretion of calprotectin in both groups. The observed increases were 48.19 ± 61.55 μg/g faeces (mean ± standard deviation) in the B420 group and 31.30 ± 39.56 μg/g in the placebo group (difference estimate 16.90; 95% confidence interval: -14.00, 47.77; P = .276). There were no significant differences between the treatment groups in changes of faecal or blood haemoglobin. Faecal B. lactis DNA was much more abundant in the B420 group compared to the placebo group (ANOVA estimate for treatment difference 0.85 × 109 /g faeces; 95% confidence interval: 0.50 × 109 , 1.21 × 109 ; P < .0001). CONCLUSIONS Short-term administration of the probiotic B420 did not protect the healthy adult study participants from diclofenac-induced gastrointestinal inflammation as determined by analysis of faecal calprotectin levels.