Efficacy of Probiotics in Prevention and Treatment of Infectious Diseases

Deaths from infectious diseases and deep concerns about increases in microbial resistance make it necessary for scientists to develop innovative therapeutic solutions and complementary therapies. Growing evidence is available on the therapeutic effects of probiotics. There are also documents about the beneficial effects of probiotics, but it is difficult to draw a definitive conclusion regarding the results of these studies because of the small sample size, the limitations of the study methods, and the use of different strains of probiotic bacteria. This review study summarizes the articles available on the scientific and electronic databases Embase, Medline, and Scopus until the end of 2017, including case studies describing beneficial microbes as tools for improving the process of controlling infectious diseases. Until the development of novel vaccines or other approaches occurs, the use of probiotics seems to be a logical way to attempt to control certain infectious diseases.     

Chronic Periodontal Disease,Periodontal Pathogen Colonization,and Increased Risk of Precancerous Gastric Lesions

Background: This study assesses the association between periodontal pathogen colonization and the potential risk of developing precancerous lesions of gastric cancer (PLGC) in a clinical setting. Methods: Included were 35 newly diagnosed patients with PLGC and 70 age‐matched individuals without PLGC. A full‐mouth intraoral examination was performed to assess periodontal conditions. Stimulated whole saliva and pooled plaque samples were collected to evaluate colonization by Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans and to characterize oral microbial diversity in saliva and dental plaque. Results: Compared with the control group, patients with PLGC experienced higher prevalence of bleeding on probing (31.5% versus 22.4%; P <0.05), higher levels of T. denticola (P <0.01) and A. actinomycetemcomitans (P <0.01), and less bacterial diversity in their saliva (P <0.01). The final multivariate logistic regression model consisting of all key sociodemographic characteristics, oral health behavioral factors, and periodontal assessments revealed that elevated colonization with periodontal pathogens, specifically T. forsythia, T. denticola, and A. actinomycetemcomitans, decreased bacterial diversity in dental plaque, and not flossing teeth regularly was a significant predictor of increased risk of PLGC (P = 0.022). Conclusion: Findings of the present study provide new evidence suggesting that periodontal pathogen burdens and bacterial diversity in the oral cavity are important factors contributing to a potentially increased risk of developing precancerous gastric lesions.     

Helios,and not FoxP3, is the marker of activated Tregs expressing GARP/LAP

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4⁺FoxP3⁻ T cells expressing Helios (FoxP3⁻Helios⁺) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4⁺Helios⁺ T cells regardless of FoxP3 expression (FoxP3^+/−Helios⁺). We show that CD4⁺GARP^+/−LAP⁺ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3⁺Helios⁺ Tregs proliferate in vitro significantly less than FoxP3⁺Helios⁻ Tregs upon TCR stimulation. Unlike FoxP3⁺Helios⁻ Tregs, FoxP3⁺Helios⁺ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3⁺Helios⁺ Tregs have more suppressive characteristics, compared with FoxP3⁺Helios⁻ Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3⁺Helios⁺ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.     

CD8+ T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a,b?/? mice favoring autoimmune cholangitis

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of unknown etiopathogenesis showing progressive autoimmune-mediated cholangitis. In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl⁻/HCO₃⁻ anion exchanger involved in biliary bicarbonate secretion and intracellular pH regulation. Decreased AE2 expression may be pathogenic as Ae2_a,b^−/− mice reproduce hepatobiliary and immunological features resembling PBC. To understand the role of AE2 deficiency for autoimmunity predisposition we focused on the phenotypic changes of T cells that occur over the life-span of Ae2_a,b^−/− mice. At early ages (1-9 months), knockout mice had reduced numbers of intrahepatic T cells, which exhibited increased activation, programmed-cell-death (PD)-1 expression, and apoptosis. Moreover, young knockouts had upregulated PD-1 ligand (PD-L1) on bile-duct cells, and administration of neutralizing anti-PD-L1 antibodies prevented their intrahepatic T-cell deletion. Older (≥10 months) knockouts, however, showed intrahepatic accumulation of cytotoxic CD8⁺ T cells with downregulated PD-1 and diminished apoptosis. In-vitro DNA demethylation with 5-aza-2′-deoxycytidine partially reverted PD-1 downregulation of intrahepatic CD8⁺ T cells from aged knockouts. Conclusion: Early in life, AE2 deficiency results in intrahepatic T-cell activation and PD-1/PD-L1 mediated deletion. With aging, intrahepatic CD8⁺ T cells epigenetically suppress PD-1, and their consequential expansion and further activation favor autoimmune cholangitis.