Placebo-resistant gut bacteria: Akkermansia muciniphila spp. and Familial Mediterranean fever disease.

Introduction: Despite numerous investigations into the impact of drugs/probiotics on the gut microbiota composition in Familial Mediterranean Fever (FMF) patients, the question as to whether there exists a significant bacterial diversity(ies) independent of the placebo effect that can be reliably considered in clinical and nutritional trials remains unresolved. Methods: This study represents the in augural analysis of the placebo's influence on the gut microbiota of both healthy individuals and FMF afflicted men, utilizing previously collected data from PhyloChip™ DNA microarray experiments. A total of 15 healthy and 15 FMF male volunteers, aged 18 to 50, participated in this partially randomized placebo trial, which is accessible through the GEO Series accession number GSE111835. Results and Discussion: Key findings from current investigations include i. the anticipated divergence in gut bacteria resistance to placebo between healthy and FMF individuals, ii. the minor impact of placebo on gut bacterial diversities in healthy individuals, with Enterobacteriaceae diversities identified as placebo-resistant among "healthy" gut bacteria, and iii. the comprehensive influence of placebo on all bacterial phyla in the gut microbiome of FMF patients, extending to nearly all bacterial genera, except for the resilience of gut Akkermansia muciniphila spp. to placebo in FMF patients. This study underscores the susceptibility of Faecalibacterium, Blautia, and Clostridium genera to placebo. Consequently, this investigation holds significance for the proper design of placebo-controlled trials and establishes a foundation for further exploration of the gut-brain axis. Furthermore, it contributes valuable insights to discussions regarding proposals for probiotic therapies, particularly focusing on Faecalibacterium spp., Blautia spp., and Clostridium spp.

Treating Leaky Syndrome in the Over 65s: Progress and Challenges.

As we age, our organ functions gradually decline. Circulating factors in the blood and the integrity of organ barriers can become dysfunctional, resulting in a condition known as leaky syndrome. This condition involves the unregulated exchange or leakage of components between organs. However, the triggers of leaky syndrome, as well as its role in aging-related disorders and illnesses, remain largely unknown. In this editorial, we discuss potential mechanisms that originate from the gut and resident microbes (microbiome) to contribute in leaky syndrome. Furthermore, we explore how the food we consume can impact the development of leaky syndrome, potentially influencing the biology of aging and challenges to diagnose the leaky gut condition accurately and clinically.

Broadcasters, receivers, functional groups of metabolites and the link to heart failure progression using polygenic factors.

In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. We identified metabolites associated with higher or lower risk of HF incidence, the associations that were not confounded by the other metabolites, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. We revealed the underlying relationships of the findings. For example, asparagine directly influenced glycine, and both were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids which are not synthesized in the human body and come directly from the diet. Metabolites may play a critical role in linking genetic background and lifestyle factors to HF progression. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates a mechanistic understanding of HF progression.

The Emerging Role of Senotherapy in Cancer: A Comprehensive Review.

Senotherapy, a promising therapeutic strategy, has drawn a lot attention recently due to its potential for combating cancer. Senotherapy refers to the targeting of senescent cells to restore tissue homeostasis and mitigate the deleterious effects associated with senescence. Senolytic drugs represent a promising avenue in cancer treatment, with the potential to target and modulate senescent cells to improve patient outcomes. The review highlights the intricate interplay between the senescence-associated secretory phenotype (SASP) and the tumor microenvironment, emphasizing the role of senescent cells in promoting chronic inflammation, immune evasion, and tumor-cell proliferation. It then explores the potential of senotherapy as a novel strategy for cancer therapy. This review addresses the emerging evidence on the combination of senotherapy with conventional cancer treatments, such as chemotherapy and immunotherapy.

Oral Microbial Signature of Rheumatoid Arthritis in Female Patients.

This study aimed to identify the oral microbial signature of Kazakh female rheumatoid arthritis (RA) patients. A total of 75 female patients who met the American College of Rheumatology 2010 classification criteria for RA and 114 healthy volunteers were included in the study. Amplicons of the 16S rRNA gene were sequenced to analyze the microbial composition. We identified significant differences in bacterial diversity and abundance between the RA and control groups, as measured by Shannon (p value = 0.0205) and Simpson (p value = 0.00152) indices. The oral samples from RA patients had higher bacterial diversity than those from non-RA volunteers. The RA samples had a higher relative abundance of Prevotellaceae and Leptotrichiaceae, but a lower content of butyrate and propionate-producing bacteria compared to the control group. The samples from patients in remission had a higher abundance of Treponema sp. and Absconditabacteriales (SR1), whereas those with low disease activity had higher levels of Porphyromonas and those with high RA activity had higher levels of Staphylococcus. A positive correlation was found between the taxa Prevotella_9 and serum levels of antibodies to cyclic citrullinated peptide (ACPA) and rheumatoid factor (RF). The predicted functional pattern of the ACPA+/RF- and ACPA+/RF+ seropositive groups was characterized by increased ascorbate metabolism, degradation of glycosaminoglycans, and reduced biodegradation of xenobiotics. These findings suggest that the functional pattern of the microflora should be considered when selecting a therapeutic strategy for RA in order to provide a personalized approach.

Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.

Natural Compounds as Integrative Therapy for Liver Protection against Inflammatory and Carcinogenic Mechanisms: From Induction to Molecular Biology Advancement.

The liver is exposed to several harmful substances that bear the potential to cause excessive liver damage ranging from hepatitis and non-alcoholic fatty liver disease to extreme cases of liver cirrhosis and hepatocellular carcinoma. Liver ailments have been effectively treated from very old times with Chinese medicinal herbal formulations and later also applied by controlled trials in Japan. However, these traditional practices have been hardly well characterized in the past till in the last decades when more qualified studies have been carried out. Modern advances have given rise to specific molecular targets which are specifically good candidates for affecting the intricate mechanisms that play a role at the molecular level. These therapeutic regimens that mainly affect the progression of the disease by inhibiting the gene expression levels or by blocking essential molecular pathways or releasing cytokines may prove to play a vital role in minimizing the tissue damage. This review, therefore, tries to throw light upon the variation in the therapies for the treatment of benign and malignant liver disease from ancient times to the current date. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of benign chronic liver diseases as well as prevention and treatment of HCC is still warranted.

Correction: Bioactive peptides derived from milk proteins and their health beneficial potentials: an update.

Correction for 'Bioactive peptides derived from milk proteins and their health beneficial potentials: an update' by Ravinder Nagpal et al., Food Funct., 2011, 2, 18-27, DOI: 10.1039/C0FO00016G.

Corrigendum to "Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases".

[This corrects the article DOI: 10.1155/2012/902917.].

Influence of Host Blood Meal Source on Gut Microbiota of Wild Caught Aedes aegypti, a Dominant Arboviral Disease Vector.

Blood feeding is an important behavior of Aedes aegypti, a dominant arboviral disease vector, as it can establish and transmit viruses to humans. Bacteria associated with the mosquito gut can modulate the biological characteristics and behavior of disease vectors. In this study, we characterized the gut microbiota composition of human-blood-fed (HF), non-human-blood-fed (NHF) and non-fed (NF) field-collected Ae. aegypti mosquitoes, using a 16S metagenomic approach, to assess any association of bacterial taxa with the blood-feeding behavior of Ae. aegypti. A significant difference in the microbiota composition between the HF and NF mosquito group was observed. A significant association was observed in the relative abundance of families Rhodobacteraceae, Neisseriaceae and Dermacoccaceae in the HF group in contrast to NF and NHF Ae. aegypti mosquitoes, respectively. At the class level, two classes (Rhodobacterales and Neisseriales) were found to be in higher abundance in the HF mosquitoes compared to a single class of bacteria (Caulobacterales) in the NF mosquitoes. These results show that human-blood feeding may change the gut microbiota in wild Ae. aegypti populations. More research is needed to determine how changes in the midgut bacterial communities in response to human-blood-feeding affect the vectorial capacity of Ae. aegypti.

Non-alcoholic fatty liver disease: correlation with hyperuricemia in a European Mediterranean population.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are two pathologies that intersect each other. It was found that there is an association between MetS/NAFLD and hyperuricemia. The aim of our study was to demonstrate this association in a European Mediterranean population. METHODS: We compared 236 patients with NAFLD to 218 patients without NAFLD. We assessed laboratory metabolic parameters (serum uric acid - SUA, fasting glucose, triglycerides, total cholesterol, etc.) and the presence or absence of MetS in a retrospective, cross-sectional, case-control manner. RESULTS: Analysis of the two main variables in study showed a moderate direct correlation (p< 0.01; Pearson coefficient 0.443) between SUA and NAFLD. Evaluation for SUA quartiles showed a decreased risk of NAFLD for the first and second quartiles (OR Q1 = 0.20; OR Q2 = 0.59), but increased for the third and fourth quartiles (OR Q3 = 2.22; OR Q4 = 6.97). In females, the risk of NAFLD was less compared to males for the first three quartiles of SUA, but it was more than double for the fourth quartile (OR Q1 0.21 vs 0.16; OR Q2 0.82 vs 0.45; OR Q3 2.50 vs 2.26; OR Q4 4.50 vs 9.83). In the NAFLD group, hyperuricemia was significantly correlated with sex, obesity, hypertension, and with the number of components of the MetS. In the Control group, SUA directly correlated with age, diabetes, and ALT, but not with obesity. CONCLUSION: We have found a significant correlation between NAFLD and hyperuricemia. The higher SUA levels accompanied the risk of NAFLD.

Triglycerides to high-density lipoprotein cholesterol ratio for diagnosing nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) is a widespread disease in the western world. It can develop into more serious pathological conditions (i.e. liver cirrhosis). Therefore, it is important to diagnose it in order to prevent this evolution. For diagnosis it is possible to use both imaging methods and biomarkers, such as the Triglycerides To High-Density Lipoprotein Cholesterol Ratio (TG/HDL-C). Aim of our study is to determine whether TG/HDL-C ratio is significantly associated with NAFLD and Metabolic Syndrome (MetS). METHODS: We recruited 231 patients, 131 with and 100 without NAFLD. The Body Mass Index had been calculated and different laboratory parameters had been obtained. TG/HDL-C ratio was calculated for each. RESULTS: In our sample HDL-C was not significantly reduced in NAFLD group (P=0.49), but higher TG and TG/HDL-C ratio were significantly associated with NAFLD: in both P<0.001. According to receiver operating characteristic curve, the best cut-off of TG/HDL-C in NAFLD population was 1.64 (area under the curve [AUC] 0.675 [95% CI 0.604-0.746], P<0.001). TG/HDL-C higher ratio was significantly associated with MetS (P<0.001). The best cut-off of TG/HDL-C in patients with MetS was 2.48 (AUC 0.871 [95% CI 0.808-0.935], P<0.001). CONCLUSIONS: We demonstrated that higher TG/HDL-C ratio is associated with NAFLD and MetS. Though nowadays TG/HDL-C ratio is not a criteria for NAFLD diagnosis, we believe that in the future it could be used as a reliable non-invasive marker in routine diagnostics of NAFLD.

A review on interplay between small RNAs and oxidative stress in cancer progression.

Oxidative stress has been known to be the underlying cause in many instances of cancer development. The new aspect of cancer genesis that has caught the attention of many researchers worldwide is its connection to non-coding RNAs (ncRNAs). ncRNAs may not be protein coding, but in light of the more recent discovery of their wide range of functions, the term 'dark matter of the genome' has been rendered inapplicable. There is an extensive mention of colon cancer as an example, where some of these ncRNAs and their manipulations have seen significant progress. As of now, the focus is on discovering a non-invasive, cost-effective method for diagnosis that is easier to monitor and can be conducted before visible symptoms indicate cancer in a patient, by which time it may already be too late. The concept of liquid biopsies has revolutionized recent diagnostic measures. It has been possible to detect circulating parts of the cancer genome or other biomarkers in the patients' bodily fluids, resulting in the effective management of the disease. This has led these ncRNAs to be considered effective therapeutic targets and extrinsic modifications in several tumor types, proven to be effective as therapy. However, there is a vast scope for further understanding and pertinent application of our acquired knowledge and expanding it in enhancing the utilization of ncRNAs for a better prognosis, quicker diagnosis, and improved management of cancer. This review explores the prognosis of cancer and related mutations by scrutinizing small ncRNAs in the disease.

FIB-4 and APRI scores for predicting severe liver fibrosis in chronic hepatitis HCV patients: a monocentric retrospective study.

AIM OF THE STUDY: Hepatitis C virus (HCV) can cause a chronic liver infection which could then develop into fibrosis, cirrhosis, and hepatocellular carcinoma. Today the diagnosis of liver fibrosis also includes the use of biomarkers. The purpose of our study was to determine the ability of the fibrosis index based on four factors (FIB-4) and aspartate aminotransferase-to-platelet ratio (APRI) to predict the severity of liver fibrosis or cirrhosis. MATERIAL AND METHODS: Medical records of 106 patients with HCV-related liver fibrosis were analyzed. All patients underwent clinical examination, blood tests (complete blood count, total bilirubin, etc.) and transient elastography. FIB-4 and APRI were calculated for each patient. RESULTS: Twenty-six patients (24.52%) had F4 fibrosis, 80 patients (75.48%) had non-F4 fibrosis (F0-F3). There was a statistically significant difference (p < 0.05) between non-F4 fibrosis patients and F4 fibrosis patients in many parameters, including APRI (F4 fibrosis patients had higher values: 2.06 ±3.22 compared to 0.68 ±0.76 of the non-F4 group; p = 0.044) and FIB-4 (F4 fibrosis patients had higher values: 4.84 ±4.14 compared to 2.29 ±2.90 of the non-F4 group; p = 0.006). Receiver operating characteristic (ROC) curve analysis for APRI and FIB-4 revealed that the area under the curve (AUC) of FIB-4 was 0.855 (CI: 0.813-0.936), while the APRI score had an AUC of 0.767 (CI: 0.79-0.932). CONCLUSIONS: In this study, patients with severe fibrosis or cirrhosis were found to have a higher FIB-4 value than APRI in the context of chronic hepatitis C.

Lactose intolerance: An update on its pathogenesis, diagnosis, and treatment.

Lactose intolerance has a high prevalence worldwide, ranging between 57% and 65%. It is caused by a reduction or loss of the activity of the intestinal enzyme lactase-phlorizin hydrolase, responsible for the digestion of lactose. This alteration determines an increased osmotic load in the small intestine and the fermentation of lactose by the bacterial flora, which leads to a high production of short-chain fatty acids and gas. This is followed by the onset of abdominal pain, diarrhea, and flatulence. In addition to these problems, it was found that subjects with lactose intolerance have an increased risk of developing various extra-intestinal diseases, including cancers. The diagnosis is essential to undertake an adequate treatment and, for this purpose, different methods have been tested. These include genetic test, hydrogen breath test (HBT), quick lactase test, and lactose tolerance test. HBT is the most used method because it is non-invasive, inexpensive, and highly sensitive and specific, as well as easy to perform. In clinical practice, the other methods are mainly used as HBT integration tests. There are also many therapeutic options. An appropriate intervention concerns the dietetic style, such as the consumption of lactose-free foods, but with nutritional characteristics comparable to dairy products. Other valid choices are represented by the use of exogenous enzymes, probiotics, prebiotics, the selection of milk containing specific types of beta-caseins. This review is intended to illustrate the diagnostic methods currently available and the possible therapeutic options for lactose intolerance.

Beyond Physical Exercise: The Role of Nutrition, Gut Microbiota and Nutraceutical Supplementation in Reducing Age-Related Sarcopenia.

Sarcopenia is a commonly prevalent geriatric condition mainly characterized by progressive loss of the skeletal muscle mass that results in noticeably reduced muscle strength and quality. Most of the geriatric population above 60 years of age are overweight, leading to the accumulation of fat in the muscles resulting in abated muscle function. The increased loss of muscle mass is associated with high rates of disability, poor motility, frailty and mortality. The excessive degeneration of muscles is now also being observed in middle-aged people. Therefore, geriatrics has recently started shifting towards the identification of early stages of the disability in order to expand the life span of the patient and reduce physical dependence. Recent findings have indicated that patients with increased physical activity are also affected by sarcopenia, therefore indicating the role of nutritional supplements to enhance muscle health which in turn helps to counteract sarcopenia. Various interventions with physical training have not provided substantial improvements to this disorder, thereby highlighting the crucial role of nutritional supplementation in enhancing muscle mass and strength. Nutritional supplementation has not only been shown to enhance the positive effects of physical interventions but also have a profound impact on the gut microbiome that has come forward as a key regulator of muscle mass and function. This brief review throws light upon the efficiency of nutrients and nutraceutical supplementation by highlighting their ancillary effects in physical interventions as well as improving the gut microbiome status in sarcopenic adults, thereby giving rise to a multimodal intervention for the treatment of sarcopenia.

Vitagenic Effect of Specific Bioactive Fractions of Rhodiola with Trachurus sp. Extract Against Oxidative Stress-Induced Aging in Human Amnion Derived Epithelial Cell Line: In View of a Novel Senolytic.

BACKGROUND: Rhodiola rosea is a herb that has been used in traditional medicine for several years, and LF is a class of lipoproteins derived from the fish Trachurus sp. (LF-T), which exhibits known anti-inflammatory activity. OBJECTIVE: Investigating the anti-aging effect of Rhodiola specific bioactive fractions cluster in combination with LF-T (R-L compound) in H2O2 mediated oxidative stress-induced human amnion derived epithelial cell line - FL cells as normal human cell line. METHODS: FL cells were treated with H2O2 to induce cellular aging, followed by treatment of the RL compound to study its anti-aging characteristics. Based on the proliferation rate, 0.05% and 0.1% concentration of R-L compound was determined using MTT assay. Anti-aging and anti-oxidant assays, ABTS, DPPH, Hyaluronidase activity Nitric Oxide, Lipid Peroxidase, and Superoxide Dismutase were performed. qPCR for anti-aging genes and matrix metalloproteinase genes were analyzed. RESULTS: FL cells treated with R-L compound exhibited increased proliferation rate and free-radical reduction. Decreased Hyaluronidase enzyme activity and regulation of genes such as SIRT1, KLOTHO, SERPINA 6, MMP 9, and MMP 2 expression depicted the anti-aging role of the R-L compound. Chemometric profiling of the R-L compound revealed that aromatic compounds and unsaturated fatty acids along with their derivatives, were present predominantly, which might have attributed to the potent oxidative stress impeded aging activity. CONCLUSION: Specific Bioactive Fractions of Rhodiola in combination with LF-T obtained from Trachurus sp. involve in the regulation of aging genes and might be a novel approach to prevent the cells from oxidative stress damage and also it might avert the aging of cells.

Impacts of ceftriaxone exposure during pregnancy on maternal gut and placental microbiota and its influence on maternal and offspring immunity in mice.

This study aimed to investigate the association between microbiota found in the maternal gut and placenta, and whether ceftriaxone exposure during pregnancy could alter these microbiota, and consequently affect the immunity of the mothers and their offspring. The microbiota in the feces and placenta of the dams were comprehensively analyzed using16S rRNA sequencing. Furthermore, viable bacteria in the placentas and blood of pups were also isolated by plate cultivation then taxonomically identified in detail by clone sequencing. Serum cytokines collected from dams and pups were quantitatively profiled using Luminex. The spleen organ index of dams was significantly lower and the offspring serum interleukin-6 levels were significantly higher in ceftriaxone-treated mice compared with the control group. The maternal fecal microbiota community was drastically altered in ceftriaxone-treated mice with significantly decreased diversity, depletion of Bacteroidetes and the blooming of Tenericutes. However, the placenta microbiota was dominated by Proteobacteria especially characteristically by Ralstonia, which was distinct from the maternal gut microbiota, regardless of whether ceftriaxone treatment or not. Viable bacteria have been found in placenta and blood cultures. These results indicated that ceftriaxone exposure in pregnancy could dramatically alter maternal intestinal microbiota, which affected the immunity of the mothers and their offspring at least partly, characteristically by enhanced pro-inflammatory responses. This study also indicated that the placenta might harbor its own microbes and the microbes were distinct from maternal gut microbiota, which may not be affected by oral administration of ceftriaxone during pregnancy.

Irritable bowel syndrome and lactose intolerance: the importance of differential diagnosis. A monocentric study.

BACKGROUND: Nowadays irritable bowel syndrome (IBS) and lactose intolerance (LI) are two very frequent diseases. IBS is a functional disorder, while LI is caused by the inability to digest lactose. LI is often incorrectly diagnosed as IBS. The aim of our study is to identify LI patients among IBS patients, so as to set up a correct therapy. METHODS: We enrolled 259 patients with IBS and we compared them to a control group of 108 patients. All patients underwent H2 Breath-Test (HBT) and two questionnaires regarding the symptoms associated with IBS and LI were administered to the intolerant subjects and one questionnaire to IBS patients with no LI. RESULTS: At the HBT, 79.9% (N.=207) of patients with IBS were positive, while in the control group were positive 25.0% (N.=27) of subjects (P<0.001). The questionnaires showed, after a month of therapy, a marked improvement in LI symptoms subjects. In addition, there was also a prevalence of more severe symptoms among subjects with IBS and LI than those with IBS and no LI. CONCLUSIONS: We can affirm that most patients with initial diagnosis of IBS are, instead, lactose intolerant. This diagnosis allows us to undertake an adequate therapy so as to improve symptoms and quality of life. Therefore it is important to include LI in the pathologies with which IBS enters into differential diagnosis.

Platelet to lymphocyte ratio as a predictive biomarker of liver fibrosis (on elastography) in patients with hepatitis C virus (HCV)-related liver disease.

BACKGROUND: Liver fibrosis is a frequent complication of chronic hepatitis C virus (HCV) infection. Its evaluation is very important for the prognosis of these patients. The aim of this study was to evaluate the possibility of exploiting the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio as non-invasive predictive markers of liver fibrosis. METHODS: We recruited 120 patients with chronic HCV infection. They were subjected to various clinical investigations to assess the severity of fibrosis. Transient elastography and some serological tests were performed, and the platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio were estimated. RESULTS: Sixty-four patients had F4 fibrosis (defined by elastography) and their platelet to lymphocyte ratio (69.92 ± 26.47) was lower than in patients with non-F4 fibrosis (95.19 ± 48.15) (p = 0.001). The neutrophil to lymphocyte ratio was also estimated, but the difference between the 2 groups of patients was not significant statistically (p = 0.07). CONCLUSION: The platelet to lymphocyte ratio can be used as a predictive biomarker of liver fibrosis, unlike the neutrophil to lymphocyte ratio which is not predictive of this HCV-related chronic hepatitis complication. More studies are needed to validate this hypothesis.