Gut microbe-host interactions in post-COVID syndrome: a debilitating or restorative partnership?

Post-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host-microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals.

Empowering probiotics with high xanthine transport for effective hyperuricemia management.

Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.

A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation.

The human microbiome is a complex and dynamic system that plays important roles in human health and disease. However, there remain limitations and theoretical gaps in our current understanding of the intricate relationship between microbes and humans. In this narrative review, we integrate the knowledge and insights from various fields, including anatomy, physiology, immunology, histology, genetics, and evolution, to propose a systematic framework. It introduces key concepts such as the 'innate and adaptive genomes', which enhance genetic and evolutionary comprehension of the human genome. The 'germ-free syndrome' challenges the traditional 'microbes as pathogens' view, advocating for the necessity of microbes for health. The 'slave tissue' concept underscores the symbiotic intricacies between human tissues and their microbial counterparts, highlighting the dynamic health implications of microbial interactions. 'Acquired microbial immunity' positions the microbiome as an adjunct to human immune systems, providing a rationale for probiotic therapies and prudent antibiotic use. The 'homeostatic reprogramming hypothesis' integrates the microbiome into the internal environment theory, potentially explaining the change in homeostatic indicators post-industrialization. The 'cell-microbe co-ecology model' elucidates the symbiotic regulation affecting cellular balance, while the 'meta-host model' broadens the host definition to include symbiotic microbes. The 'health-illness conversion model' encapsulates the innate and adaptive genomes' interplay and dysbiosis patterns. The aim here is to provide a more focused and coherent understanding of microbiome and highlight future research avenues that could lead to a more effective and efficient healthcare system.

Mechanisms of action of Lactobacillus spp. in the treatment of oral candidiasis.

Candida albicans is often associated with oral candidiasis, and drug-resistance profiles have contributed to an increase in morbidity and mortality. It is known that Lactobacillus spp. acts by competing for adhesion to the epithelium, absorption of nutrients and modulation of the human microbiota. Therefore, they are important to assist in the host's microbiological balance and reduce the growth of Candida spp. Until now, there have been no reports in the literature of reviews correlating to the use of Lactobacillus spp. in the treatment of oral candidiasis. Thus, this review aims to highlight the mechanisms of action of Lactobacillus spp. and methods that can be used in the treatment of oral candidiasis. This is a study carried out through the databases PubMed Central and Scientific Electronic Library Online, using the following keywords: Oral Candidiasis and Lactobacillus. Original articles about oral candidiasis were included, with both in vitro and in vivo analyses, and published from 2012 to 2022. Lactobacillus rhamnosus was the most common microorganism used in the experiments against Candida, acting mainly in the reduction of biofilm, filamentation, and competing for adhesion sites of Candida spp. Among in vivo studies, most researchers used immunosuppressed mouse modelsof Candida infection. The studies showed that Lactobacillus has a great potential as a probiotic, acting mainly in the prevention and treatment of mucosal diseases. Thus, the use of Lactobacillus may be a good strategy for the treatment of oral candidiasis.

Evaluation of efficacy and safety of Lacticaseibacillus rhamnosus LRa05 in the eradication of Helicobacter pylori: a randomized, double-blind, placebo-controlled trial.

Aim: This study aims to evaluate the efficacy of Lacticaseibacillus rhamnosus LRa05 supplementation in enhancing Helicobacter pylori (H. pylori) eradication rate and alleviating the gastrointestinal side effects associated with bismuth quadruple therapy. Methods: H. pylori-positive patients were randomized to receive levofloxacin-based bismuth quadruple therapy combined either probiotic LRa05 or a placebo for two weeks, followed by LRa05 (1 × 1010 CFU) or maltodextrin for the next two weeks. H. pylori infection was detected by 13C breath test pre- and post-treatment. Blood and stool samples were collected at week 0 and week 4 for routine and biochemical analysis, and serum inflammatory markers. Gastrointestinal symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS). Intestinal microbiota was analyzed using 16S rRNA sequencing. The research was listed under the Chinese Clinical Trial Registry (ChiCTR2300072220), and written informed consent was obtained from all participants. Results: The LRa05 group exhibited a trend toward higher H. pylori eradication rates (86.11%) compared to the placebo group (82.86%), though the difference was not statistically significant. Significant reductions in neutrophil count, alanine aminotransferase, aspartate aminotransferase, pepsinogen I, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) (p < 0.05) suggest that LRa05 supplementation may mitigate inflammation, enhance liver function, and potential aid in early cancer prevention. GSRS symptom scores showed that LRa05 alleviated abdominal pain, acid reflux, bloating, and diarrhea, enhancing patient compliance. Furthermore, 16S rRNA sequencing showed that LRa05 countered the antibiotic-induced disruption of gut microbiota diversity, primarily by increasing beneficial bacteria. Conclusion: Although LRa05 did not significantly improve the success rate of H. pylori eradication therapy, it has the potential to improve liver function and reduced levels of inflammatory markers such as IL-6 and TNF-α in the body, regulating the inflammatory response. In addition, it played a positive role in alleviating the adverse symptoms and gut microbiota disturbances caused by eradication therapy, providing a possible way to improve the overall health of patients and demonstrating promising clinical potential. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2300072220.

Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections.

SCOPE: The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals & pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum & other bacterial spp. reduce IFNγ & TNF-α and increase IL-4 & IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. CONCLUSION: The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities.

Assessment of the Prophylactic Effects of Probiotics, Prebiotics, and Synbiotics Against COVID-19 Infection: A Systematic Review of Randomized Controlled Trials.

Background: Although various treatments are developed against COVID-19 variants, probiotic, and synbiotic adjunct therapy with several benefits such as safety, low cost, and availability could be needed for preventing or treating COVID-19 infection.Objective: The present systematic review aimed to assess the prophylactic efficacy of the probiotic, prebiotic, and synbiotic administration against COVID-19.Methods: The protocol of this systematic review was registered at the PROSPERO (Code number: CRD42023418900). The Scopus, Cochrane Library, Web of Sciences, and PubMed databases were systematically searched to define the clinical trials published up to November 2022 in the English language. The comparison of the incidence of COVID-19 disease and levels of specific antibodies against SARS-cov2 between the intervention and placebo groups were evaluated in this systematic review.Results: According to the five included trials, four indicated the incidence of COVID-19, and no significant differences were observed between the probiotic and placebo groups during 1, 2, or 3 months of follow-up in the mentioned studies. Regarding the antibody assays against SARS-Cov2 including IgM, IgG, or IgA reported by three eligible trials, there were no significant differences between the intervention and control groups.Conclusion: It seems that the administration of single or multi-strain probiotics or synbiotics had no prophylactic effects in different populations such as high-risk staff exposed to COVID-19, elderly nursing home residents, healthy adults, and household contact with COVID-19 patients during 1-to-3-months of intervention.

Broadening horizons: intestinal microbiota as a novel biomarker and potential treatment for hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP.

Probiotics and magnesium orotate for the treatment of major depressive disorder: a randomised double blind controlled trial.

Following on from our pilot studies, this study aimed to test the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate and coenzyme 10 for the treatment of major depressive disorder (MDD) through a double-blind placebo controlled clinical trial. The participants were 120 adults diagnosed with MDD randomised to daily oral administration, over 8 weeks, of either the intervention or placebo, with a 16-week follow-up period. Intent-to-treat analysis found a significantly lower frequency of the presence of a major depressive episode in the intervention group compared with placebo at the end of the 8-week treatment phase, with no difference between the two conditions at 8-week follow-up. Both the categorical and continuous measure of depressive symptoms showed a significant difference between the two conditions at 4 weeks, but not 8 and 16 weeks. The secondary end-point was demonstrated with an overall reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo. These findings suggest that the combination of probiotics, magnesium orotate and coenzyme 10 may be an effective treatment of MDD over an 8-week period.

Comparative evaluation of antimicrobial efficacy of various intracanal medicament in young permanent teeth: An in vivo study.

INTRODUCTION: Bacteria and their byproducts are key contributors to the onset and perpetuation of pulpoperiapical pathosis. Intracanal medication is vital in achieving successful endodontic outcomes as it targets and eradicates remaining microorganisms following biomechanical preparation. AIM AND OBJECTIVE: The aim of the study was to compare and evaluate the antimicrobial efficacy of calcium hydroxide (CH) paste, triple antibiotic paste (TAP), and probiotics (PBs) as intracanal medicament in 12-17-year-old children undergoing root canal treatment for the management of infected pulpal tissues in young permanent teeth. MATERIALS AND METHODS: A total of 30 patients aged 12-17 years indicated for endodontic therapy in maxillary incisors and with no systemic complications were selected. They were randomly divided into three groups, i.e., Group I - CH group, Group II - TAP, and Group III - PB allocating 10 teeth in each group. After access opening, the first sample (S1) was collected by inserting a paper point into the root canal, the second sample (S2) was collected immediately after biomechanical preparation, and the third sample (S3) was collected after 7 days, i.e., postintracanal medication. Samples were sent for microbiological analysis to assess the microbial count, and statistical analysis was done for the obtained data. RESULTS: The three intracanal medicaments were successful in reducing the microbial counts of Enterococcus faecalis in the infected root canals. However, according to the results of the study, the PB group demonstrated greater effectiveness against E. faecalis compared to the CH group and displayed similar antimicrobial efficacy as the TAP group. CONCLUSION: PB exhibited antimicrobial efficacy comparable to TAP but greater than Ca (OH) 2 paste. Hence, PB can be utilized as an intracanal medicament in young permanent teeth.

Probiotics and Fecal Microbiota Transplantation in Major Depression: Doxa or Episteme?

In the human body, eukaryotic somatic cells and prokaryotic microorganisms live together. In this state, the body can be viewed as a "superorganism." Symbiotic life with commensal microorganisms can be observed in almost every part of the body. Intestinal microbiota plays an important role in health and disease, and in shaping and regulating neuronal functions from the intrauterine period to the end of life. Microbiota-based treatment opportunities are becoming more evident in both understanding the etiopathogenesis and treatment of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first choice in the treatment of depression, also have antimicrobial and immunomodulatory mechanisms of action. From these perspectives, direct probiotics and fecal microbiota transplantation are treatment options to modulate microbiota composition. There are few preclinical and clinical studies on the effectiveness and safety of these applications in depression. The information obtained from these studies may still be at a doxa level. However, the probability that this information will become episteme in the future seems to be increasing.

Combining Complementary and Alternative Medicine (CAM) with Conventional Treatments for Major Depressive Disorder.

For many of the complementary and alternative (CAM) medicine methods, it is biologically plausible to expect that they could provide additional benefits in the treatment of major depressive disorder (e.g., enhanced initial response, augmentation, and tolerability) when combined with conventional treatments. Although most likely not comprehensively, herein we critically review current explicit clinical data pertaining to the most extensively evaluated CAMs in this setting: physical activity/exercise, mind and body methods, acupuncture, light therapy, diet, probiotics, various nutrients, and herbal preparations. While the absolute amount of data is enormous, the number of reliable primary studies (randomized controlled trials) and, particularly, meaningful meta-analyses of such studies are very limited. Consequently, the certainty of evidence about benefit or no benefit is very low for each of the addressed CAMs.

The Mechanisms and Application Value of Postbiotics in Caries Prevention and Management.

Dental caries, one of the most prevalent diseases globally, affects individuals throughout their lifetimes. Recently, researchers have increasingly focused on postbiotics for caries prevention. Postbiotics, comprising inanimate microorganisms and/or their components, confer health benefits to the host. Growing evidence suggests postbiotics' potential anticaries effects. Specifically, numerous postbiotics have demonstrated the ability to inhibit dental caries onset and progression by modulating oral flora microecology and reducing human caries susceptibility. This review elaborates on the current research regarding postbiotics' anticaries effects, highlights some studies' shortcomings, and innovatively proposes that postbiotics could potentially influence tooth development and salivary characteristics through epigenetic modifications. Furthermore, it anticipates postbiotics' future application in personalised caries treatment, given their multifaceted anticaries potential.

A case report of diet elimination guided by food specific IgG4 achieved clinical cure for eczematous external otitis with finger paronychia.

RATIONALE: Eczematous external otitis (EEO) is the most difficult-to-treat otitis externa, and characterized by the symptoms of inflammation with hypersensitivity of the external ear canal skin. It is acknowledged as a chronic skin inflammation primarily caused by dermatological and allergic reactions. Food allergens are also considered a cause to induce the inflammation. However, the role of food specific IgG4 in this disease is unclear yet. PATIENT CONCERNS: A 54-year-old woman complained of recurrent itching of the external auditory meatus for 3 years and nails chapping of hands for 2 years. DIAGNOSES AND INTERVENTIONS: She was diagnosed with EEO and underwent the therapeutic strategy as food elimination of egg, milk and wheat, guided by the result of food specific IgG4 together with probiotics on the basis of previous symptom controlling therapy. OUTCOMES: After 17 months' treatment, she was finally free of all the symptoms and the serum IgG4 specific to all foods are under normal limit. LESSONS: To the best of our knowledge, it is the first report revealing the clinical significance of food specific IgG4 in EEO, and the successful treatment with diet elimination guided by food specific IgG4 threw a new light on the clinical management of refractory EEO.

Gut microbiota dysbiosis and its impact on asthma and other lung diseases: potential therapeutic approaches.

The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.

Impact of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 Probiotic Supplementation on the Gut Microbiome of Hypercholesterolemia Patients: A Randomized Controlled Trial.

Probiotics have shown potential in managing hypercholesterolemia and related metabolic conditions. This study evaluated the effects of Lactocaseibacillus (Lactobacillus) paracasei sup. paracasei TISTR 2593 on the gut microbiome and metabolic health in patients with hypercholesterolemia, and was registered in the Thai Clinical Trial Registry (TCTR 20220917002). In a randomized, double-blind, placebo-controlled trial, 22 hypercholesterolemic participants received either the probiotic or a placebo daily for 90 days. Fecal samples collected before and after the intervention revealed significant microbiome changes, including a decrease in Subdoligranulum, linked to rheumatoid arthritis, and an increase in Flavonifractor, known for its anti-inflammatory properties. Additionally, the probiotic group exhibited a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels. These findings suggest that L. paracasei TISTR 2593 can modulate the gut microbiome and improve metabolic health, warranting further investigation into its mechanisms and long-term benefits.

Impact of Clinical Use of Probiotics on Preterm-Related Outcomes in Infants with Extremely Low Birth Weight.

Background: Preterm birth significantly contributes to mortality and morbidities, with recent studies linking these issues to gut microbiota imbalances. Probiotic supplementation shows promise in mitigating adverse outcomes in preterm infants, but optimal timing and guidelines remain unclear. This study assesses the benefits of probiotic supplementation for preterm infants without consistent guidelines. Methods: This retrospective study examined extremely low-birth-weight (ELBW) infants in neonatal intensive care units from 2017 to 2021. Mortality and preterm-related outcomes were compared between infants receiving probiotics and those not. Subgroup analyses based on probiotic initiation timing were conducted: early (≤14 days), late (>14 days), and non-probiotic groups. Results: The study included 330 ELBW infants: 206 received probiotics (60 early, 146 late), while 124 did not. Probiotic supplementation was associated with lower overall mortality (adjusted OR 0.22, 95% CI 0.09-0.48) and decreased mortality from necrotizing enterocolitis (NEC) or late-onset sepsis (LOS) (adjusted OR 0.12, 95% CI 0.03-0.45). Early probiotics reduced overall mortality, NEC/LOS-related mortality, and NEC/LOS-unrelated mortality. Late probiotics decreased overall mortality and NEC/LOS-related mortality. Early probiotic use also expedited full enteral feeding achievement. Conclusions: Probiotic supplementation reduces mortality and improves feeding tolerance in preterm infants. Establishing guidelines for probiotic use in this population is crucial.