A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris.

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted. The study product was a capsule composed of the probiotic Lacticaseibacillus rhamnosus (CECT 30031) and the cyanobacterium Arthrospira platensis (BEA_IDA_0074B). Patients with improvement in the Acne Global Severity Scale were 10/34 (29.41%) in the placebo group compared with 20/40 (50%) in the probiotic group (p = 0.03). A significant reduction (p = 0.03) in the number of non-inflammatory acne lesions was observed in the probiotic group (-18.60 [-24.38 to -12.82]) vs the placebo group (-10.54 [-17.43 to -3.66]). Regarding the number of total  lesions, a reduction almost reaching statistical significance (p = 0.06) was observed in the probiotic group (-27.94 [-36.35 to -19.53]) compared with the placebo group (-18.31 [-28.21 to -8.41]). In addition, patients with improvement attending the Global Acne Grading System were 7/34 (20.58%) in the placebo group vs 17/40 (42.50%) in the probiotic group (p = 0.02). The number of adverse events was similar in both groups. The probiotic used in this study was effective and well tolerated, and it should be considered for acne vulgaris patients.

Bladder Cancer and Probiotics: What Do We Know So Far?

Bladder cancer is around the 10th most diagnosed cancer, although has a considerable mortality. Recent research and new methodologies have discarded the historical dogma that the bladder (and urine) was sterile under normal conditions. Specifically, only a few studies have reported a detailed analysis of the urinary microbiota in patients with bladder cancer, thus exhibiting a remarkable variability due to the low biomass of the urinary microbiota and the influence of many factors. Nevertheless, this research shows us signals that urinary microbiota is a factor to be considered in the pathophysiology of bladder cancer. More importantly, probiotics could be useful as an adjuvant therapy to reduce the recurrence rate or increase the disease-free period after surgery. In vitro studies and animal assays have shown promising results, but the research in this context has also been scarce, and only a few studies have been conducted in humans. In summary, there is little evidence of the possible beneficial effect of probiotics in controlling the overgrowth of genera that could be involved in the carcinogenesis of bladder cancer. This narrative review aims to compile all the evidence to date on the therapeutic potential of probiotics injected directly into the bladder or orally administered.

Randomized double-blind placebo-controlled clinical trial to evaluate the effect of a mixture of probiotic strains on symptom severity and use of corticosteroids in children and adolescents with atopic dermatitis.

BACKGROUND: The intestinal microbiota is altered in patients with atopic dermatitis (AD) when compared with those of the healthy population. Some interventions with specific probiotic preparations already demonstrate a change in composition of this microbiota accompanied by improvement in the disease. OBJECTIVES: This research work was designed to evaluate clinical efficacy of the probiotic preparation, and to measure the effect of the intervention on the total dose of corticosteroids administered to subjects. METHODS: This double-blind, randomized, placebo-controlled clinical trial including 70 participants with AD aged 4-17 years was designed to evaluate the clinical effect, compared with placebo, of a probiotic mixture of Bifidobacterium lactis, Bifidobacterium longum and Lactobacillus casei at a total daily consumption of 1 × 109 colony-forming units per capsule, over 12 weeks. After randomization and exclusion, 35 patients were allocated to probiotic and 35 to placebo. Clinical variables analysed were SCORAD (SCORing of Atopic Dermatitis) and Investigator Global Assessment (IGA) indices; effect on the amount of topical corticosteroids used; and assessment of safety. RESULTS: Mean SCORAD index at 12 weeks showed a statistically significant difference of -5.43 (95% confidence interval -10.65 to -0.21) between probiotic (SCORAD 13.52) and placebo groups (SCORAD 18.96); P = 0.04. Comparison between groups showed a statistically significant difference in the number of patients with IGA score improvement over the 12-week intervention: 29 of 32 (90.5%) in the probiotic group vs. 17 of 30 (56.7%) in the placebo group (P < 0.002). A comparison between groups of the proportions of days using corticosteroids and the total dose (g) of corticosteroids between baseline and end of study showed no significant difference, but between weeks 6 and 12 there was a statistically significant reduction in the probiotic group when compared with the placebo group in both variables. Numbers of adverse events were similar in both groups of treatment. CONCLUSIONS: The probiotic mix used in this clinical trial demonstrated efficacy on the change in activity index of AD compared with placebo. Furthermore, the total number of days and total amount of topical corticosteroids required by participants in the probiotic group showed a significant reduction compared with placebo between 6 and 12 weeks.

Role of microbiome in kidney stone disease.

PURPOSE OF REVIEW: The process of renal stone formation is complex, multifactorial, and variable depending on the type of stone. The microbiome, whether by direct or indirect action, is a factor that both promotes the formation and protects from developing of renal stones. It is a highly variable factor due to the great interindividual and intraindividual variability that it presents. In recent years, with the incorporation of nonculture-based techniques such as the high-throughput sequencing of 16S rRNA bacterian gene, both intestinal and urinary microbiota have been deeply studied in various diseases such as the kidney stone disease. RECENT FINDINGS: This review has examined the new insights on the influence of the intestinal and urinary microbiome in nephrolithiasis disease and its usefulness as a diagnostic and prognostic tool, highlighting its contribution to the pathogenesis, its ability to modulate it and to influence disease development. SUMMARY: The incidence of urolithiasis has been increasing considerably. These patients represent a significant expense for national health systems. With the knowledge of the influence of the urobiome and intestinal microbiota on the urolithiasis, it could be possible to modulate it to interrupt its development.

Rosacea, microbiome and probiotics: the gut-skin axis.

Rosacea is an inflammatory skin disease involving diverse symptoms with a variable clinical progress which can severely impact the patient's quality of life as well as their mental health. The pathophysiological model of rosacea involves an unbalanced immune system predisposed to excessive inflammation, in addition to vascular and nervous alterations, being certain cutaneous microorganisms' triggers of the symptoms onset. The gut-skin axis explains a bidirectional interaction between skin and gut microbiota in some inflammatory skin diseases such as atopic dermatitis, psoriasis, or rosacea. The introduction and consolidation of the next-generation sequencing in recent years has provided unprecedented information about the microbiome. However, the characterization of the gut and skin microbiota and the impact of the gut-skin axis in patients with rosacea has been little explored, in contrast to other inflammatory skin diseases such as atopic dermatitis or psoriasis. Furthermore, the clinical evolution of patients with rosacea is not always adequate and it is common for them to present a sustained symptomatology with frequent flare-ups. In this context, probiotic supplementation could improve the clinical evolution of these patients as happens in other pathologies. Through this review we aim to establish and compile the basics and directions of current knowledge to understand the mechanisms by which the microbiome influences the pathogenesis of rosacea, and how modulation of the skin and gut microbiota could benefit these patients.

How Our Microbiome Influences the Pathogenesis of Alopecia Areata.

Alopecia areata is a multifactorial autoimmune-based disease with a complex pathogenesis. As in all autoimmune diseases, genetic predisposition is key. The collapse of the immune privilege of the hair follicle leading to scalp loss is a major pathogenic event in alopecia areata. The microbiota considered a bacterial ecosystem located in a specific area of the human body could somehow influence the pathogenesis of alopecia areata, as it occurs in other autoimmune diseases. Moreover, the Next Generation Sequencing of the 16S rRNA bacterial gene and the metagenomic methodology have provided an excellent characterization of the microbiota. The aim of this narrative review is to examine the published literature on the cutaneous and intestinal microbiota in alopecia areata to be able to establish a pathogenic link. In this review, we summarize the influence of the microbiota on the development of alopecia areata. We first introduce the general pathogenic mechanisms that cause alopecia areata to understand the influence that the microbiota may exert and then we summarize the studies that have been carried out on what type of gut and skin microbiota is found in patients with this disease.

Oral intake of Kluyveromyces marxianus B0399 plus Lactobacillus rhamnosus CECT 30579 to mitigate symptoms in COVID-19 patients: A randomized open label clinical trial.

At the beginning of the SARS-CoV-2 pandemic, developing of new treatments to control the spread of infection and decrease morbidity and mortality are necessary. This prospective, open-label, case-control intervention study evaluates the impact of the oral intake of the probiotic yeast Kluyveromyces marxianus B0399 together with Lactobacillus rhamnosus CECT 30579, administered for 30 days, on the evolution of COVID-19 patients. Analysis of the digestive symptoms at the end of the follow up shows a benefit of the probiotic in the number of patients without pyrosis (100% vs 33.3%; p 0.05) and without abdominal pain (100% vs 62.5%; p 0.04). Results also show a better evolution when evaluating the difference in the overall number of patients without non-digestive symptoms at the end of the follow-up (41.7%, vs 13%; p 0.06). The percentage of improvement in the digestive symptoms (65% vs 88%; p value 0.06) and the global symptoms (digestive and non-digestive) (88.6% vs 70.8%; p value 0.03) is higher in the probiotic group. The probiotic was well tolerated with no relevant side effects and high adherence among patients. In conclusion, this coadjutant treatment seems to be promising, although results should be confirmed in new studies with higher number of patients.

Acne, Microbiome, and Probiotics: The Gut-Skin Axis.

The objective of this narrative review was to check the influence of the human microbiota in the pathogenesis of acne and how the treatment with probiotics as adjuvant or alternative therapy affects the evolution of acne vulgaris. Acne is a chronic inflammatory skin disease involving the pilosebaceous units. The pathogenesis of acne is complex and multifactorial involving genetic, metabolic, and hormonal factors in which both skin and gut microbiota are implicated. Numerous studies have shown the bidirectionality between the intestinal microbiota and skin homeostasis, a communication mainly established by modifying the immune system. Increased data on the mechanisms of action regarding the relevance of Cutibacterium acnes, as well as the importance of the gut-skin axis, are becoming known. Diverse and varied in vitro studies have shown the potential beneficial effects of probiotics in this context. Clinical trials with both topical and oral probiotics are scarce, although they have shown positive results, especially with oral probiotics through the modulation of the intestinal microbiota, generating an anti-inflammatory response and restoring intestinal integrity, or through metabolic pathways involving insulin-like growth factor I (IGF-1). Given the aggressiveness of some standard acne treatments, probiotics should continue to be investigated as an alternative or adjuvant therapy.

Gut Microbiota as a Potential Predictive Biomarker in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: The influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in patients with multiple sclerosis (MS). The role of this dysbiosis is still unknown. OBJECTIVE: We analyzed the gut microbiota of 15 patients with active relapsing-remitting multiple sclerosis (RRMS), comparing with diet-matched healthy controls. METHOD: To determine the composition of the gut microbiota, we performed high-throughput sequencing of the 16S ribosomal RNA gene. The specific amplified sequences were in the V3 and V4 regions of the 16S ribosomal RNA gene. RESULTS: The gut microbiota of RRMS patients differed from healthy controls in the levels of the Lachnospiraceae, Ezakiella, Ruminococcaceae, Hungatella, Roseburia, Clostridium, Shuttleworthia, Poephyromonas, and Bilophila genera. All these genera were included in a logistic regression analysis to determine the sensitivity and the specificity of the test. Finally, the ROC (receiver operating characteristic) and AUC with a 95% CI were calculated and best-matched for Ezakiella (AUC of 75.0 and CI from 60.6 to 89.4) and Bilophila (AUC of 70.2 and CI from 50.1 to 90.4). CONCLUSIONS: There is a dysbiosis in the gut microbiota of RRMS patients. An analysis of the components of the microbiota suggests the role of some genera as a predictive factor of RRMS prognosis and diagnosis.

Selection of Probiotics in the Prevention of Respiratory Tract Infections and Their Impact on Occupational Health: Scoping Review.

The occupational health impact of respiratory infectious diseases is costly to the economy and the health care system. Probiotics are non-pathogenic live microorganisms that, when ingested in adequate amounts, can colonize the intestinal tract, and enhance the immune system. In recent years, numerous studies have described the possible usefulness of certain probiotic strains in the treatment and prevention of respiratory tract infections, with disparate results. In order to assess the possible efficacy and safety of these microorganisms to prevent or ameliorate respiratory tract infections, we systematically searched the bibliographic databases MEDLINE (via Pubmed), EMBASE, The Cochrane library, Scopus, and Web of science, using the descriptors "Respiratory Tract Infections", "Probiotics", "Occupational Health", "Humans", and "Clinical Trials". After applying our inclusion and exclusion criteria, 18 studies were accepted for review and critical analysis. Our analysis suggests that a combination of different probiotics, most of them in the genus Bifidobacterium sp. and Lactobacillus sp., could be a good mix to strengthen the immune system and reduce the symptoms of URTIs in the healthy working population.

Probiotics in the Therapeutic Arsenal of Dermatologists.

During the last years, numerous studies have described the presence of significant gut and skin dysbiosis in some dermatological diseases such as atopic dermatitis, psoriasis and acne, among others. How the skin and the gut microbiome play a role in those skin conditions is something to explore, which will shed light on understanding the origin and implication of the microbiota in their pathophysiology. Several studies provide evidence for the influence of probiotic treatments that target the modulation of the skin and intestinal microbiota in those disorders and a positive influence of orally administered probiotics on the course of these dermatosis. The pathologies in which the therapeutic role of the probiotic has been explored are mainly atopic dermatitis, psoriasis and acne. This article aims to review these three dermatological diseases, their relationship with the human microbiota and specially the effect of probiotics usage. In addition, the pathophysiology in each of them and the hypotheses about possible mechanisms of the action of probiotics will be described.

Descriptive Study of Gut Microbiota in Infected and Colonized Subjects by Clostridiodes difficile.

Clostridiodes difficile can lead to a range of situations from the absence of symptoms (colonization) to severe diarrhea (infection). Disruption of gut microbiota provides an ideal environment for infection to occur. Comparison of gut microbiota of infected and colonized subjects could provide relevant information on susceptible groups or protectors to the development of infection, since the presence of certain genera could be related to the inhibition of transition from a state of colonization to infection. Through high-throughput sequencing of 16S rDNA gene, we performed alpha and beta diversity and composition studies on 15 infected patients (Group CDI), 15 colonized subjects (Group P), and 15 healthy controls (Group CTLR). A loss of alpha diversity and richness and a different structure have been evidenced in the CDI and P groups with respect to the CTRL group, but without significant differences between the first two. In CDI and P groups, there was a strong decrease in phylum Firmicutes and an expansion of potential pathogens. Likewise, there was a loss of inhibitory genus of C. difficile germination in infected patients that were partially conserved in colonized subjects. Therefore, infected and colonized subjects presented a gut microbiota that was completely different from that of healthy controls, although similar to each other. It is in composition where we found that colonized subjects, especially in minority genera, presented differences with respect to those infected.

Reference ranges for serum and salivary testosterone in young men of Mediterranean region / Valores de referencia de testosterona sérica y salivar en varones jóvenes del área Mediterránea

BACKGROUND AND AIMS: The interassay variability found in the measurement of testosterone (T) levels warrants the need for laboratories to validate their methods to establish trustworthy cut-off points for diagnosis of male hypogonadism. The aims of this study were to validate measurement of total T (TT) at our laboratory in order to obtain reference ranges for TT, calculated free T (CFT), calculated bioavailable T (CBT), and salivary T (ST) in healthy young men from the Mediterranean region, and to evaluate the potential clinical value of ST by establishing its correlation with serum T. METHODS: An observational, cross-sectional study with sequential sampling. Inclusion criteria: men aged 18-30 years with body mass index (BMI) < 30. Exclusion criteria: chronic diseases, hepatic insufficiency or use of drugs altering circulating T levels. Main outcome measures TT (chemiluminescent immunoassay UniCell DXI 800 [Access T Beckman Coulter]), CFT and CBT (Vermeulen's formula), and ST (radioimmunoassay for serum TT modified for saliva [Coat-A-Count, Siemens]). Descriptive statistical analyses and correlation by Spearman's rho (SPSS 19.0 Inc., Chicago) were used. RESULTS: One hundred and twenty-one subjects aged 24 ± 3.6 years with BMI 24 ± 2.5 kg/m2 were enrolled. Hormone study: TT, 19 ± 5.5 nmol/L (reference range [rr.] 9.7-33.3); CFT, 0.38 nmol/L (rr. 0.22-0.79); CBT, 9.7 nmol/L (rr. 4.9-19.2); and ST, 0.35 nmol/L (rr. 0.19-0.68). Correlation between ST and CFT was 0.46. CONCLUSIONS: In men from the Mediterranean region, values of TT > 9.7 nmol/L, CFT > 0.22 nmol/L, and/or CBT > 4.9 nmol/L make the presence of biochemical hypogonadism unlikely. According to the correlation between serum and ST, the clinical value of ST remains to be established

ANTECEDENTES Y OBJETIVOS: La variabilidad interensayo existente en la determinación de testosterona (T) justifica la necesidad de que cada laboratorio valide su método y establezca puntos de corte fiables para el diagnóstico del hipogonadismo masculino. Los objetivos del estudio fueron validar la determinación de T total (TT) en nuestro laboratorio para obtener los valores de referencia de TT, T libre calculada (TLC), T biodisponible calculada (TBC) y T salivar (TS) en varones jóvenes sanos del área mediterránea y evaluar la posible utilidad clínica de la TS. MATERIAL Y MÉTODOS: Estudio observacional transversal. Muestreo secuencial. CRITERIOS DE INCLUSIÓN: varones, 18-30 años de edad, índice de masa corporal (IMC) < 30. Criterios de exclusión: enfermedades crónicas, insuficiencia hepática o uso de medicamentos que alteran las concentraciones circulantes de T. METODOLOGÍA: TT (inmunoanálisis de quimioluminiscencia UniCell DXI800 [Acces T Beckman Coulter]), TLC y TBC (fórmula de Vermeulen), TS (radioinmunoensayo para TT sérica modificado para la saliva [Coat-A-Count, Siemens]). Análisis estadísticos: descriptivos y correlación rho de Spearman (SPSS 19,0 Inc.,Chicago). RESULTADOS: Se incluyeron 121 individuos de 24 ± 3,6 años e IMC 24 ± 2,5 kg/m2. Estudio hormonal TT, 19 ± 5,5 nmol/L (intervalo de confianza 95% 9,7-33,3); TLC, 0,38 nmol/L ([P2,5-P97,5] 0,22-0,79); TBC, 9,7 nmol/L ([P2,5-P97,5] 4,9-19,2); y TS, 0,35 nmol/L ([P2,5-P97,5] 0,19-0,68). La correlación entre TS y TLC fue 0,46. CONCLUSIONES: En varones de la región mediterránea, concentraciones de TT > 9,7 nmol/L, TLC > 0,22 nmol/L y/o TBC > 4,9 nmol/L hacen improbable la presencia de hipogonadismo bioquímico. De acuerdo a la correlación entre la testosterona sérica y salivar, la utilidad clínica de la ST está aún por establecerse

Reference ranges for serum and salivary testosterone in young men of Mediterranean region.

BACKGROUND AND AIMS: The interassay variability found in the measurement of testosterone (T) levels warrants the need for laboratories to validate their methods to establish trustworthy cut-off points for diagnosis of male hypogonadism. The aims of this study were to validate measurement of total T (TT) at our laboratory in order to obtain reference ranges for TT, calculated free T (CFT), calculated bioavailable T (CBT), and salivary T (ST) in healthy young men from the Mediterranean region, and to evaluate the potential clinical value of ST by establishing its correlation with serum T. METHODS: An observational, cross-sectional study with sequential sampling. INCLUSION CRITERIA: men aged 18-30 years with body mass index (BMI)<30. EXCLUSION CRITERIA: chronic diseases, hepatic insufficiency or use of drugs altering circulating T levels. Main outcome measures TT (chemiluminescent immunoassay UniCell DXI 800 [Access T Beckman Coulter]), CFT and CBT (Vermeulen's formula), and ST (radioimmunoassay for serum TT modified for saliva [Coat-A-Count, Siemens]). Descriptive statistical analyses and correlation by Spearman's rho (SPSS 19.0 Inc., Chicago) were used. RESULTS: One hundred and twenty-one subjects aged 24±3.6 years with BMI 24±2.5 kg/m(2) were enrolled. Hormone study: TT, 19±5.5 nmol/L (reference range [rr.] 9.7-33.3); CFT, 0.38 nmol/L (rr. 0.22-0.79); CBT, 9.7 nmol/L (rr. 4.9-19.2); and ST, 0.35 nmol/L (rr. 0.19-0.68). Correlation between ST and CFT was 0.46. CONCLUSIONS: In men from the Mediterranean region, values of TT>9.7 nmol/L, CFT>0.22 nmol/L, and/or CBT>4.9 nmol/L make the presence of biochemical hypogonadism unlikely. According to the correlation between serum and ST, the clinical value of ST remains to be established.

Presentación atípica de un caso de fiebre mediterránea familiar / Atypical presentation of a case of familial mediterranean fever

La fiebre mediterránea familiar (FMF) es un síndrome hereditario de fiebre periódica caracterizada por ataques cortos de fiebre e inflamación multisistémica (poliserositis y sinovitis, principalmente). El desarrollo de amiloidosis, sobre todo renal, es la principal complicación. Los síntomas aparecen, en la mayoría de casos, antes de la segunda década de vida. Se trata de una enfermedad hereditaria monogénica y el gen asociado se llama MEFV. El diagnóstico genético puede ser de gran ayuda, aunque existen aspectos que todavía no están claros. En un porcentaje muy pequeño de pacientes, la enfermedad aparece de una forma atípica, es decir, más tardía e iniciando con amiloidosis, sin existir antecedente de ataques previos inflamatorios o fiebres periódicas. Es el fenotipo II de la FMF. Presentamos el caso de un varón de 24 años con amiloidosis renal que cumple estas características, donde el estudio genético resultó clave para el diagnóstico (AU)

Familial Mediterranean Fever is a periodic hereditary fever syndrome characterised by short fever attacks and multisystemic inflammation (mainly polyserositis and synovitis). The main complication is development of amyloidosis, particularly renal. In the majority of cases, symptoms appear before the age of twenty. It is a monogenic hereditary disease that is related to the MEFV gene. A genetic diagnosis may be helpful, although there are some aspects that are still not clear enough. A small percentage of patients present an atypical form, appearing later and debuting with amyloidosis but without any previous inflammatory attacks or periodic fevers. This form is Familial Mediterranean Fever phenotype II. We present the case of a 24 year-old with renal amyloidosis that presents these characteristics and in whom the genetic study was fundamental for the diagnosis (AU)