Fewer Community-Acquired Colds with Daily Consumption of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2. A Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Viral infections of the upper airways are the most common cause for absence from work or school, and there is evidence for probiotic efficacy in reducing the incidence and severity of these infections. OBJECTIVES: We aimed to confirm the previously reported beneficial effects of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 against community-acquired common colds and identify a possible mechanism of action. METHODS: In a double-blind study, healthy adults (18-70 years of age) with at least 4 colds during the last 12 months before recruitment were randomly allocated to consume either probiotics (n = 448; total daily dose of 109 CFU with the 2 strains equally represented) or placebo (n = 450) once daily for 12 weeks. Recruitment took place from October to February during 2013-2016 (over 3 cold seasons). The probiotic impact on the severity of the colds (Wisconsin Upper Respiratory Symptom Survey-21) was the primary endpoint, whereas secondary endpoints included the incidence rate and duration of colds and an analysis of immune markers. Mann-Whitney U test and mixed model were used for the analysis of continuous variables and Fisher´s exact test was used for the analysis of categorical endpoints. RESULTS: Symptom severity was not reduced after intake of the probiotic, despite the positive trend seen in the first season. However, significantly fewer colds were experienced in the probiotic group (mean of 1.24 colds) as compared to the placebo group (mean of 1.36 colds; P = 0.044) for subjects reporting at least 1 cold, the incidence of recurring colds was 30% lower (20.8% vs. 29.8%, respectively; P = 0.055), and the use of analgesics was 18% lower (26.3% vs. 32%, respectively; P = 0.07). After 12 weeks, the change from baseline for IFN-γ differed between the groups (mean difference of -7.01; 95% CI, -14.9 to 0.93; P = 0.045). CONCLUSIONS: Intake of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 can be protective against multiple colds in adults prone to getting colds.This trial was registered at clinicaltrials.gov as NCT02013934.

Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha.

Impaired oxidative phosphorylation is suggested as a factor behind insulin resistance of skeletal muscle in type 2 diabetes. The role of oxidative phosphorylation in adipose tissue was elucidated from results of Affymetrix gene profiling in subcutaneous and visceral adipose tissue of eight nonobese healthy, eight obese healthy, and eight obese type 2 diabetic women. Downregulation of several genes in the electron transport chain was the most prominent finding in visceral fat of type 2 diabetic women independent of obesity, but the gene pattern was distinct from that previously reported in skeletal muscle in type 2 diabetes. A similar but much weaker effect was observed in subcutaneous fat. Tumor necrosis factor-alpha (TNF-alpha) is a major factor behind inflammation and insulin resistance in adipose tissue. TNF-alpha treatment decreased mRNA expression of electron transport chain genes and also inhibited fatty acid oxidation when differentiated human preadipocytes were treated with the cytokine for 48 h. Thus, type 2 diabetes is associated with a tissue- and region-specific downregulation of oxidative phosphorylation genes that is independent of obesity and at least in part mediated by TNF-alpha, suggesting that impaired oxidative phosphorylation of visceral adipose tissue has pathogenic importance for development of type 2 diabetes.

A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects.

CONTEXT: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood. OBJECTIVES: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion. DESIGN: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human s.c. adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts. RESULTS: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation. CONCLUSIONS: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.

A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity.

Elevated circulating fatty acid concentration is a hallmark of insulin resistance and is at least in part attributed to the action of adipose tissue-derived tumor necrosis factor-alpha (TNF-alpha) on lipolysis. Cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) belongs to a family of proapoptotic proteins that has five known members in humans and mice. The action of CIDEA is unknown, but CIDEA-null mice are resistant to obesity and diabetes. We investigated CIDEA in adipose tissue of obese and lean humans and mice. The mRNA was expressed in white human fat cells and in brown mouse adipocytes. The adipose mRNA expression of CIDEA in mice was not influenced by obesity. However, CIDEA expression was decreased twofold in obese humans and normalized after weight reduction. Low adipose CIDEA expression was associated with several features of the metabolic syndrome. Human adipocyte depletion of CIDEA by RNA interference stimulated lipolysis and increased TNF-alpha secretion by a posttranscriptional effect. Conversely, TNF-alpha treatment decreased adipocyte CIDEA expression via the mitogen-activated protein kinase c-Jun NH(2)-terminal kinase. We propose an important and human-specific role for CIDEA in lipolysis regulation and metabolic complications of obesity, which is at least in part mediated by cross-talk between CIDEA and TNF-alpha.