Current landscape of fecal microbiota transplantation in treating depression.

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.

Impact of high-salt diet in health and diseases and its role in pursuit of cancer immunotherapy by modulating gut microbiome.

Cancer chemotherapy remains an area of concern, as many of the therapies are uncomfortable involving side effects and unpleasant experiences. These factors could further reduce patient's quality of life, and even endanger their life. Many therapeutic strategies have been tried to reduce the unpleasant side effects and increase the treatment effectiveness; however, none have shown to have promising effects. One of the main hindrances to cancer therapy is the escape strategies by tumor cells to the immune attack. Promoting inflammation in the tumor microenvironment is the cornerstone and key therapeutic target in cancer chemotherapy. High-salt diet (HSD) intake, though it has deleterious effects on human health by promoting chronic inflammation, is found to be advantageous in the tumor microenvironment. Studies identified HSD favors an increased abundance of Bifidobacterium species in the tumor environment due to gut barrier alteration, which, in turn, promotes inflammation and favors improved response to cancer chemotherapy. A review of the literature was carried out to find out the effects of an HSD on health and diseases, with special mention of its effect on cancer chemotherapy. Studies emphasized HSD would block the myeloid-derived suppressor cells which will enhance the tumor immunity. Exploration of the precise mechanism of simple HSD regime/ingestion of specific bacterial species as probiotics will be effective and essential to formulate the game-changing cancer chemotherapy. With the modern era of healthcare moving toward precision medicine where the physician can choose the treatment option suitable for the individual, HSD regime/ingestion of specific bacterial species can be considered.

Role of gut microbiota and immune cells in metabolic-associated fatty liver disease: clinical impact.

In 2020, a revised definition of fatty liver disease associated with metabolic dysfunction (MAFLD) was proposed to replace non-alcoholic fatty liver (NAFLD). Liver steatosis and at least one of the three metabolic risk factors, including type 2 diabetes, obesity, or signs of metabolic dysregulation, are used to diagnose MAFLD. MAFLD, similarly to NAFLD, is characterized by a spectrum of disease ranging from simple steatosis to advanced metabolic steatohepatitis with or without fibrosis, and may progress to cirrhosis and liver cancer, including increased risk of other critical extrahepatic diseases. Even though the pathophysiology of MAFLD and potential therapeutic targets have been explored in great detail, there is yet no Food and Drug Administration approved treatment. Recently, gut microbiome-derived products (e.g., endotoxins and metabolites) involved in intestinal barrier disruption, systemic inflammation, and modification of intrahepatic immunity have been associated with MAFLD development and progression. Therefore, different strategies could be adopted to modify the gut microbiome to improve outcomes in early and progressive MAFLD. Here, we provide an overview of mechanisms that may link the gut microbiome and immune response during the onset of liver steatosis and progression to steatohepatitis and fibrosis in patients with MAFLD. Finally, gut microbiota-based approaches are discussed as potential personalized treatments against MAFLD.

How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation.

The gut microbiome has come to prominence across research disciplines, due to its influence on major biological systems within humans. Recently, a relationship between the gut microbiome and hematopoietic system has been identified and coined the gut-bone marrow axis. It is well established that the hematopoietic system and gut microbiome separately alter with age; however, the relationship between these changes and how these systems influence each other demands investigation. Since the hematopoietic system produces immune cells that help govern commensal bacteria, it is important to identify how the microbiome interacts with hematopoietic stem cells (HSCs). The gut microbiota has been shown to influence the development and outcomes of hematologic disorders, suggesting dysbiosis may influence the maintenance of HSCs with age. Short chain fatty acids (SCFAs), lactate, iron availability, tryptophan metabolites, bacterial extracellular vesicles, microbe associated molecular patterns (MAMPs), and toll-like receptor (TLR) signalling have been proposed as key mediators of communication across the gut-bone marrow axis and will be reviewed in this article within the context of aging.

Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adipose-liver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and FMT. Understanding the immunological mechanisms underlying in SLD is crucial for advancing clinical therapeutic strategies.

Vitamin D3 supplementation in COVID-19 patients with cardiovascular disease and gut dysbiosis.

BACKGROUND: The COVID-19 pandemic has highlighted the vulnerability of particular patient groups to SARS-CoV-2 infection, including those with cardiovascular diseases, hypertension, and intestinal dysbiosis. COVID-19 affects the gut, suggesting diet and vitamin D3 supplementation may affect disease progression. AIMS: To evaluate levels of Ang II and Ang-(1-7), cytokine profile, and gut microbiota status in patients hospitalized for mild COVID-19 with a history of cardiovascular disease and treated with daily doses of vitamin D3. METHODS: We recruited 50 adult patients. We screened 50 adult patients and accessed pathophysiology study 22, randomized to daily oral doses of 10,000IU vitamin D3 (n=11) or placebo (n=11). Plasma levels of Ang II and Ang-(1-7) were determined by radioimmunoassay, TMA and TMAO were measured by liquid chromatography and interleukins (ILs) 6, 8, 10 and TNF-α by ELISA. RESULTS: The Ang-(1-7)/Ang II ratio, as an indirect measure of ACE2 enzymatic activity, increased in the vitamin D3 group (24±5pg/mL vs. 4.66±2pg/mL, p<0.01). Also, in the vitamin D3-treated, there was a significant decline in inflammatory ILs and an increase in protective markers, such as a substantial reduction in TMAO (5±2µmoles/dL vs. 60±10µmoles/dL, p<0.01). In addition, treated patients experienced less severity of infection, required less intensive care, had fewer days of hospitalization, and a reduced mortality rate. Additionally, improvements in markers of cardiovascular function were seen in the vitamin D3 group, including a tendency for reductions in blood pressure in hypertensive patients. CONCLUSIONS: Vitamin D3 supplementation in patients with COVID-19 and specific conditions is associated with a more favourable prognosis, suggesting therapeutic potential in patients with comorbidities such as cardiovascular disease and gut dysbiosis.

Probiotics an emerging therapeutic approach towards gut-brain-axis oriented chronic health issues induced by microplastics: A comprehensive review.

Applications for plastic polymers can be found all around the world, often discarded without any prior care, exacerbating the environmental issue. When large waste materials are released into the environment, they undergo physical, biological, and photo-degradation processes that break them down into smaller polymer fragments known as microplastics (MPs). The time it takes for residual plastic to degrade depends on the type of polymer and environmental factors, with some taking as long as 600 years or more. Due to their small size, microplastics can contaminate food and enter the human body through food chains and webs, causing gastrointestinal (GI) tract pain that can range from local to systemic. Microplastics can also acquire hydrophobic organic pollutants and heavy metals on their surface, due to their large surface area and surface hydrophobicity. The levels of contamination on the microplastic surface are significantly higher than in the natural environment. The gut-brain axis (GB axis), through which organisms interact with their environment, regulate nutritional digestion and absorption, intestinal motility and secretion, complex polysaccharide breakdown, and maintain intestinal integrity, can be altered by microplastics acting alone or in combination with pollutants. Probiotics have shown significant therapeutic potential in managing various illnesses mediated by the gut-brain axis. They connect hormonal and biochemical pathways to promote gut and brain health, making them a promising therapy option for a variety of GB axis-mediated illnesses. Additionally, taking probiotics with or without food can reduce the production of pro-inflammatory cytokines, reactive oxygen species (ROS), neuro-inflammation, neurodegeneration, protein folding, and both motor and non-motor symptoms in individuals with Parkinson's disease. This study provides new insight into microplastic-induced gut dysbiosis, its associated health risks, and the benefits of using both traditional and next-generation probiotics to maintain gut homeostasis.

The Effect of Type 2 Resistant Starch and Indole-3-Propionic Acid on Ameliorating High-Fat-Diet-Induced Hepatic Steatosis and Gut Dysbiosis.

Owing to the interplay of genetic and environmental factors, obesity has emerged as a significant global public health concern. To gain enhanced control over obesity, we examined the effects of type 2 resistant starch (RS2) and its promoted microbial-derived metabolite, indole-3-propionic acid (IPA), on hepatic steatosis, antioxidant activity, and gut microbiota in obese mice. Neither RS2 nor low-dose IPA (20 mg kg-1) exhibited a reduction in body weight or improved glucose and lipid metabolism in post-obesity state mice continuously fed the high-fat diet (HFD). However, both interventions improved hepatic steatosis, with RS2 being more effective in all measured parameters, potentially due to changes in gut microbiota and metabolites not solely attributed to IPA. LC-MS/MS analysis revealed increased serum IPA levels in both RS2 and IPA groups, which positively correlated with Bifidobacterium and Clostridium. Moreover, RS2 exhibited a more significant restoration of gut dysbiosis by promoting the abundance of health-promoting bacteria including Faecalibaculum and Bifidobacterium. These findings suggest that the regulatory role of RS2 on tryptophan metabolism only partially explains its prebiotic activity. Future studies should consider increasing the dose of IPA and combining RS2 and IPA to explore their potential interventions in obesity.

Periodontal Inflammation and Dysbiosis Relate to Microbial Changes in the Gut.

Periodontal disease (PerioD) is a chronic inflammatory disease of dysbiotic etiology. Animal models and few human data showed a relationship between oral bacteria and gut dysbiosis. However, the effect of periodontal inflammation and subgingival dysbiosis on the gut is unknown. We hypothesized that periodontal inflammation and its associated subgingival dysbiosis contribute to gut dysbiosis even in subjects free of known gut disorders. We evaluated and compared elderly subjects with Low and High periodontal inflammation (assessed by Periodontal Inflamed Surface Area (PISA)) for stool and subgingival derived bacteria (assayed by 16S rRNA sequencing). The associations between PISA/subgingival dysbiosis and gut dysbiosis and bacteria known to produce short-chain fatty acid (SCFA) were assessed. LEfSe analysis showed that, in Low PISA, species belonging to Lactobacillus, Roseburia, and Ruminococcus taxa and Lactobacillus zeae were enriched, while species belonging to Coprococcus, Clostridiales, and Atopobium were enriched in High PISA. Regression analyses showed that PISA associated with indicators of dysbiosis in the gut mainly reduced abundance of SCFA producing bacteria (Radj = -0.38, p = 0.03). Subgingival bacterial dysbiosis also associated with reduced levels of gut SCFA producing bacteria (Radj = -0.58, p = 0.002). These results suggest that periodontal inflammation and subgingival microbiota contribute to gut bacterial changes.

Gut Permeability and Immune-Mediated Inflammation in Heart Failure.

Heart failure (HF) is characterized by low-grade immune-mediated inflammation due to increased Toll-like receptor (TLR) expression as response to endotoxin increase and dysregulated gut barrier permeability. We investigated TLR expression and possible gut dysbiosis in HF patients compared to a control group. We enrolled 80 Caucasian HF patients and 20 controls. Low-grade immune-mediated inflammation was evaluated by TLR expression, while gut dysbiosis by the detection of zonulin and bacterial endotoxin activity in a semi-quantitative (endotoxin activity assay [EAA]) and quantitative (limulus amebocyte lysate [LAL] test) way. Compared to controls, patients with HF showed significantly higher age and blood pressure values, worse metabolic profile and kidney function, higher inflammatory biomarkers levels, and lower levels of zonulin and endotoxin activity. When dividing failing patients in those with reduced ejection fraction (HF-rEF) and those with preserved ejection fraction (HF-pEF), HF-rEF patients showed significantly higher values of inflammatory biomarkers and TLR expression than HF-pEF patients. Gut permeability biomarkers inversely correlated with the severity of HF and positively with renal function. eGFR was retained as an independent predictor of zonulin variation in all the three groups of failing patients. Present data work to extend current knowledge about the role of gut microbiota in immune-mediated inflammation in HF.

Antibiotic-induced gut microbe dysbiosis alters neurobehavior in mice through modulation of BDNF and gut integrity.

Gut microbiota is essential for intestinal integrity and brain functions. Herein we aimed to investigate the effects of alteration of gut microbiome using broad-spectrum antibiotics on CD 1 male mice (germ-modified group (GM). Moreover, we co-administrated probiotics with or without antibiotics for four weeks and evaluated if probiotics could reverse these behavioral and intestinal effects. GM, co-administered antibiotics and probiotics, and probiotics-only groups were compared to control mice of the same sex, age, and weight that did not receive either drug (n=12 in all groups). Cultivation of aerobic and anaerobic bacteria was evaluated by fecal culture of all groups. We tested exploratory behavior, anxiety, memory, depression-like behavior, and hippocampal and frontal lobe BDNF protein level alterations in response to antibiotics and its downstream effect on the PI3K/Akt1/Bcl2 pathway. Intestinal integrity was evaluated using gene expression analysis of ZO-1, claudin, and occludin genes. Additionally, the inflammatory TLR4 and p-p38 MAPK pathways in the intestines were investigated. Twice-daily administration of oral antibiotics for four weeks significantly reduced total bacterial count and upregulated TLR4 and p-p38.GM mice showed a significant reduction in BDNF(P =0.04), impaired spatial memory, and long-term memory as evidenced by decreased T maze correct alternation trails and shortened retention time in the passive avoidance test in GM(P =0.01). Passive avoidance showed significantly increased latency after probiotics intake. Depressive-like behavior was more pronounced in GM mice as assessed by the tail suspension test (P =0.01). GM showed significant upregulation(p<0.001) of the TLR4 and p-p38 MAPK pathway. Co-administration of probiotics with antibiotics showed an increase in BDNF levels, and upregulation of the cell survival PI3K/Akt1/Bcl2 pathway, significantly higher relative abundance in the firmucutes members, a significant decrease in the Firmicutes/Bacteroidetes ratio and downregulation of TLR4 and p-p38 MAPK. The tight junction proteins ZO-1, claudin and occludin were downregulated by antibiotic administration for four weeks and restored by probiotics. Collectively, the data suggest that long-term use of antibiotics appears to disrupt the intestinal epithelial barrier and alter neurobehavioral qualities specifically, long-term memory and exploratory drive, possibly through the reduction of BDNF, and probiotics partially reverse these effects. Our study emphasizes the effect of prolonged intake of antibiotics on production of dysbiosis as well as the impact of the antibiotic induced intestinal inflammation on neurobehavioral aspects in mice as the memory and anxiety-like behavior. We also reveal that co-administration of probiotics can reverse these changes.

Vertical Transfer of Maternal Gut Microbes to Offspring of Western Diet-Fed Dams Drives Reduced Levels of Tryptophan Metabolites and Postnatal Innate Immune Response.

Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by the dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition and was associated with a reduced abundance of Lactobacillus in GF offspring. Further, the expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, highlighting the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and the development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice.

BACKGROUND: High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD). RESULTS: C57BL/6 mice (5-6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. Bacteroidetes, Firmicutes, and Proteobacteria were highly abundant in C-HFD group, while the Verrucomicrobia, Saccharibacteria (TM7), Actinobacteria, and Tenericutes were more abundant in F-HFD group. Other taxa in C-HFD group included the Bacteroides, Odoribacter, Sutterella, Firmicutes bacterium (AF12), Anaeroplasma, Roseburia, and Parabacteroides distasonis. An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (Acaca), Fatty acid synthase (Fasn), Stearoyl-CoA desaturase-1 (Scd1), Elongation of long-chain fatty acids family member 6 (Elovl6), Peroxisome proliferator-activated receptor-gamma (Pparg) and cholesterol synthesis (ß-(hydroxy ß-methylglutaryl-CoA reductase (Hmgcr). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (CD36), Fatty acid binding protein-1 (Fabp1) and efflux (ATP-binding cassette G1 (Abcg1), Microsomal TG transfer protein (Mttp) in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (Tnfa), C-C motif chemokine ligand 2 (Ccl2), and Interleukin-12 (Il12), as well as a tendency for liver fibrosis. CONCLUSION: These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance.

Intermittent fasting induced cerebral ischemic tolerance altered gut microbiome and increased levels of short-chain fatty acids to a beneficial phenotype.

Preconditioning-induced cerebral ischemic tolerance is known to be a beneficial adaptation to protect the brain in an unavoidable event of stroke. We currently demonstrate that a short bout (6 weeks) of intermittent fasting (IF; 15 h fast/day) induces similar ischemic tolerance to that of a longer bout (12 weeks) in adult C57BL/6 male mice subjected to transient middle cerebral artery occlusion (MCAO). In addition, the 6 weeks IF regimen induced ischemic tolerance irrespective of age (3 months or 24 months) and sex. Mice subjected to transient MCAO following IF showed improved motor function recovery (rotarod and beam walk tests) between days 1 and 14 of reperfusion and smaller infarcts (T2-MRI) on day 1 of reperfusion compared with age/sex matched ad libitum (AL) controls. Diet influences the gut microbiome composition and stroke is known to promote gut bacterial dysbiosis. We presently show that IF promotes a beneficial phenotype of gut microbiome following transient MCAO compared with AL cohort. Furthermore, post-stroke levels of short-chain fatty acids (SCFAs), which are known to be neuroprotective, are higher in the fecal samples of the IF cohort compared with the AL cohort. Thus, our studies indicate the efficacy of IF in protecting the brain after stroke, irrespective of age and sex, probably by altering gut microbiome and SCFA production.

Gastrointestinal Biofilms: Endoscopic Detection, Disease Relevance, and Therapeutic Strategies.

Gastrointestinal biofilms are highly heterogenic and spatially organized polymicrobial communities that can expand and cover large areas in the gastrointestinal tract. Gut microbiota dysbiosis, mucus disruption, and epithelial invasion are associated with pathogenic biofilms that have been linked to gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel diseases, gastric cancer, and colon cancer. Intestinal biofilms are highly prevalent in ulcerative colitis and irritable bowel syndrome patients, and most endoscopists will have observed such biofilms during colonoscopy, maybe without appreciating their biological and clinical importance. Gut biofilms have a protective extracellular matrix that renders them challenging to treat, and effective therapies are yet to be developed. This review covers gastrointestinal biofilm formation, growth, appearance and detection, biofilm architecture and signalling, human host defence mechanisms, disease and clinical relevance of biofilms, therapeutic approaches, and future perspectives. Critical knowledge gaps and open research questions regarding the biofilm's exact pathophysiological relevance and key hurdles in translating therapeutic advances into the clinic are discussed. Taken together, this review summarizes the status quo in gut biofilm research and provides perspectives and guidance for future research and therapeutic strategies.

Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation.

Gut-dysbiosis-induced lipopolysaccharides (LPS) translocation into systemic circulation has been suggested to be implicated in nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to assess if oleuropein (OLE), a component of extra virgin olive oil, lowers high-fat-diet (HFD)-induced endotoxemia and, eventually, liver steatosis. An immunohistochemistry analysis of the intestine and liver was performed in (i) control mice (CTR; n = 15), (ii) high-fat-diet fed (HFD) mice (HFD; n = 16), and (iii) HFD mice treated with 6 µg/day of OLE for 30 days (HFD + OLE, n = 13). The HFD mice developed significant liver steatosis compared to the controls, an effect that was significantly reduced in the HFD + OLE-treated mice. The amount of hepatocyte LPS localization and the number of TLR4+ macrophages were higher in the HFD mice in the than controls and were lowered in the HFD + OLE-treated mice. The number of CD42b+ platelets was increased in the liver sinusoids of the HFD mice compared to the controls and decreased in the HFD + OLE-treated mice. Compared to the controls, the HFD-treated mice showed a high percentage of intestine PAS+ goblet cells, an increased length of intestinal crypts, LPS localization and TLR4+ expression, and occludin downregulation, an effect counteracted in the HFD + OLE-treated mice. The HFD-fed animals displayed increased systemic levels of LPS and zonulin, but they were reduced in the HFD + OLE-treated animals. It can be seen that OLE administration improves liver steatosis and inflammation in association with decreased LPS translocation into the systemic circulation, hepatocyte localization of LPS and TLR4 downregulation in HFD-induced mouse model of NAFLD.

COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Role of Anti-Inflammatory Diet and Fecal Microbiota Transplant in Psoriatic Arthritis.

PURPOSE: Psoriatic arthritis (PsA) is a chronic inflammatory condition with complex and heterogenous manifestations. Although a myriad of treatment options including biologic medications are available to alleviate symptoms and slow disease progression, there is currently no cure for this condition. There has been a recent emergence of understanding about the relationship between the gut microbiome and immune-mediated inflammatory diseases. This has generated interest in the potential role of dietary interventions, particularly anti-inflammatory diets, and fecal microbiota transplant (FMT) as novel therapeutic approaches. The purpose of this narrative review is to examine the role of an anti-inflammatory diet and FMT in turn and whether their combination may offer alternate approaches for the management of PsA. METHODS: Our non-systematic narrative review was informed by a literature search using PubMed and Google Scholar using the terms anti-inflammatory diet, FMT, nutrition supplements, and PsA. Preclinical studies and non-English language articles were excluded when synthesizing the narrative review. FINDINGS: Current randomized controlled trials (RCTs) and observational evidence suggest that a hypocaloric diet or Mediterranean diet can help achieve weight loss among PsA patients who are overweight or obese, which in turn reduces inflammation and improves disease activity. However, there is no strong data to support the beneficial effects of intermittent fasting, vitamin supplements, turmeric supplements, probiotics, or omega-3 fatty acid supplements in PsA. Current evidence on the use of FMT in PsA is limited as only one small RCT has been conducted which did not demonstrate efficacy for improving clinical symptoms. IMPLICATIONS: Clinicians can consider recommending hypocaloric or Mediterranean diets as an adjunct to standard management of PsA, possibly under the guidance of a dietician. Further research is needed to explore the beneficial effects of the synergistic role of combining an anti-inflammatory diet with FMT in PsA.

Polycystic ovary syndrome: Insights into its prevalence, diagnosis, and management with special reference to gut microbial dysbiosis.

Polycystic ovary syndrome (PCOS) represents major endocrine and metabolic disorder among women largely characterized by hyperandrogenism and oligomenorrhea precipitates serious complications such as type 2 diabetes, early atherosclerosis, infertility, and endometrial cancer. Several etiological theories were proposed to define the exact cause of the PCOS, which is characterized, by the hypothalamic-pituitary axis, ovarian morphology, and release of adrenal steroid hormones, metabolic syndrome, and hereditary factors. The review explored the role of dysbiosis and the mechanisms through which microbial dysbiosis can affect PCOS development. In recent time, various research groups highlighted the role of microbial gut dysbiosis associated with obesity as potential etiological factor for the PCOS. In the present review, we reviewed the mechanisms attributed to the microbial dysbiosis and treatment approaches to deal with the situation.

"Does the Gut microbiome influence disc health and disease?-the interplay between dysbiosis, pathobionts, and disc inflammation: a Pilot Study".

BACKGROUND CONTEXT: Gut microbiome alterations resulting in inflammatory responses have been implicated in many distant effects on different organs. However, its influence on disc health is still not fully investigated. PURPOSE: Our objective was to document the gut biome in healthy volunteers and patients with disc degeneration and to understand the role of gut dysbiosis on human disc health. STUDY DESIGN: Experimental case-control study. PATIENT SAMPLE: We included 40 patients with disc degeneration (DG) and 20 healthy volunteers (HV). HV comprised of age groups 30 to 60 years with no known record of back pain and no clinical comorbidities, with normal MRI. Diseased group (DG) were patients in the same age group undergoing surgery for disc disease (disc herniation-25; discogenic stenosis-15) and without instability (with Modic-20; and non-Modic-20). OUTCOME MEASURES: N/A. METHODS: We analyzed 16S V3-V4 rDNA gut metagenome from 20 healthy volunteers (HV) and compared the top signature genera from 40 patients with disc degeneration (DG) across Modic and non-Modic groups. Norgen Stool DNA Kit was used for DNA extraction from ∼200 mg of each faecal sample collected using the Norgen Stool Collection Kit.16S V3-V4 rDNA amplicons were generated with universal bacterial primers 341F and 806R and amplified with Q5 High-Fidelity DNA Polymerase. Libraries were sequenced with 250×2 PE to an average of 0.1 million raw reads per sample (Illumina Novaseq 6000). Demultiplexed raw data was assessed with FastQC, and adapter trimmed reads >Q30 reads were processed in the QIME2 pipeline. Serum C-reactive protein (CRP) was measured by the immunoturbimetry method and Fatty acid-binding protein 5 (FABP5) was measured in albumin-globulin-depleted plasma through global proteome analysis. RESULTS: We observed significant gut dysbiosis between HV and DG and also between the Modic and non-Modic groups. In the Modic group, commensals Bifidobacterium and Ruminococcus were significantly depleted, while pathobionts Streptococcus, Prevotella, and Butryvibrio were enriched. Firmicutes/Bacteroidetes ratio was decreased in DG (Modic-0.62, non-Modic-0.43) compared to HV (0.70). Bacteria-producing beneficial short-chain fatty acids were also depleted in DG. Elevated serum CRP and increased FABP5 were observed in DG. CONCLUSION: The study revealed gut dysbiosis, an altered Firmicutes/Bacteroidetes ratio, reduced SCFA-producing bacteria, and increased systemic and local inflammation in association with disc disease, especially in Modic changes. The findings have considerable importance for our understanding and prevention of disc degeneration.