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The potential of probiotics in the amelioration of hyperuricemia.
Zhao, H, Lu, Z, Lu, Y
Food & function. 2022;(5):2394-2414
Abstract
Hyperuricemia is a common disease caused by metabolic disorders or the excessive intake of high-purine foods. Persistent hyperuricemia in extreme cases induces gout, and asymptomatic hyperuricemia is probably linked to other metabolic diseases, such as hypertension. The typical damage caused by asymptomatic hyperuricemia includes inflammation, oxidative stress and gut dysbiosis. Probiotics have broad potential applications as food additives, not as drug therapies, in the amelioration of hyperuricemia. In this review, we describe novel methods for potential hyperuricemia amelioration with probiotics. The pathways through which probiotics may ameliorate hyperuricemia are discussed, including the decrease in uric acid production through purine assimilation and XOD (xanthine oxidase) inhibition as well as enhanced excretion of uric acid production by promoting ABCG2 (ATP binding cassette subfamily G member 2) activity, respectively. Three possible probiotic-related therapeutic pathways for alleviating the syndrome of hyperuricemia are also summarized. The first mechanism is to alleviate the oxidation and inflammation induced by hyperuricemia through the inhibition of NLRP3 inflammasome, the second is to restore damaged intestinal epithelium barriers and prevent gut microbiota dysbiosis, and the third is to enhance the innate immune system by increasing the secretion of immunoglobulin A (sIgA) to resist the stimulus by hyperuricemia. We propose that future research should focus on superior strain resource isolation and insight into the cause-effect mechanisms of probiotics for hyperuricemia amelioration. The safety and effects of the application of probiotics in clinical use also need verification.
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Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial.
Kragsnaes, MS, Kjeldsen, J, Horn, HC, Munk, HL, Pedersen, JK, Just, SA, Ahlquist, P, Pedersen, FM, de Wit, M, Möller, S, et al
Annals of the rheumatic diseases. 2021;(9):1158-1167
Abstract
OBJECTIVES Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). METHODS In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. RESULTS Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). CONCLUSIONS In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. TRIAL REGISTRATION NUMBER NCT03058900.
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The Role of DNA Damage Response in Dysbiosis-Induced Colorectal Cancer.
Rivas-Domínguez, A, Pastor, N, Martínez-López, L, Colón-Pérez, J, Bermúdez, B, Orta, ML
Cells. 2021;(8)
Abstract
The high incidence of colorectal cancer (CRC) in developed countries indicates a predominant role of the environment as a causative factor. Natural gut microbiota provides multiple benefits to humans. Dysbiosis is characterized by an unbalanced microbiota and causes intestinal damage and inflammation. The latter is a common denominator in many cancers including CRC. Indeed, in an inflammation scenario, cellular growth is promoted and immune cells release Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), which cause DNA damage. Apart from that, many metabolites from the diet are converted into DNA damaging agents by microbiota and some bacteria deliver DNA damaging toxins in dysbiosis conditions as well. The interactions between diet, microbiota, inflammation, and CRC are not the result of a straightforward relationship, but rather a network of multifactorial interactions that deserve deep consideration, as their consequences are not yet fully elucidated. In this paper, we will review the influence of dysbiosis in the induction of DNA damage and CRC.
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Intestinal Microbiota as a Contributor to Chronic Inflammation and Its Potential Modifications.
Potrykus, M, Czaja-Stolc, S, Stankiewicz, M, Kaska, Ł, Małgorzewicz, S
Nutrients. 2021;(11)
Abstract
The gut microbiota is a crucial factor in maintaining homeostasis. The presence of commensal microorganisms leads to the stimulation of the immune system and its maturation. In turn, dysbiosis with an impaired intestinal barrier leads to accelerated contact of microbiota with the host's immune cells. Microbial structural parts, i.e., pathogen-associated molecular patterns (PAMPs), such as flagellin (FLG), peptidoglycan (PGN), lipoteichoic acid (LTA), and lipopolysaccharide (LPS), induce inflammation via activation of pattern recognition receptors. Microbial metabolites can also develop chronic low-grade inflammation, which is the cause of many metabolic diseases. This article aims to systematize information on the influence of microbiota on chronic inflammation and the benefits of microbiota modification through dietary changes, prebiotics, and probiotic intake. Scientific research indicates that the modification of the microbiota in various disease states can reduce inflammation and improve the metabolic profile. However, since there is no pattern for a healthy microbiota, there is no optimal way to modify it. The methods of influencing microbiota should be adapted to the type of dysbiosis. Although there are studies on the microbiota and its effects on inflammation, this subject is still relatively unknown, and more research is needed in this area.
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Gut Microbial Metabolite-Mediated Regulation of the Intestinal Barrier in the Pathogenesis of Inflammatory Bowel Disease.
Iyer, N, Corr, SC
Nutrients. 2021;(12)
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease. The disease has a multifactorial aetiology, involving genetic, microbial as well as environmental factors. The disease pathogenesis operates at the host-microbe interface in the gut. The intestinal epithelium plays a central role in IBD disease pathogenesis. Apart from being a physical barrier, the epithelium acts as a node that integrates environmental, dietary, and microbial cues to calibrate host immune response and maintain homeostasis in the gut. IBD patients display microbial dysbiosis in the gut, combined with an increased barrier permeability that contributes to disease pathogenesis. Metabolites produced by microbes in the gut are dynamic indicators of diet, host, and microbial interplay in the gut. Microbial metabolites are actively absorbed or diffused across the intestinal lining to affect the host response in the intestine as well as at systemic sites via the engagement of cognate receptors. In this review, we summarize insights from metabolomics studies, uncovering the dynamic changes in gut metabolite profiles in IBD and their importance as potential diagnostic and prognostic biomarkers of disease. We focus on gut microbial metabolites as key regulators of the intestinal barrier and their role in the pathogenesis of IBD.
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Gut microbiota in dementia. Critical review of novel findings and their potential application.
Łuc, M, Misiak, B, Pawłowski, M, Stańczykiewicz, B, Zabłocka, A, Szcześniak, D, Pałęga, A, Rymaszewska, J
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110039
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Abstract
There is a great deal of impetus for the comprehensive understanding of the complete pathological function, genetic information, and functional diversity of the gut microbiota that favors the development of dementia. It has been reported that patients with mild cognitive impairment and Alzheimer's disease present with several metabolic and immune-inflammatory alterations. The recently highlighted aspects of human health linked to cognitive decline include insulin-resistance, obesity, and chronic low-grade inflammation. Gut microbiota is known to produce neurotransmitters, such as GABA, acetylcholine, dopamine or serotonin, vitamins, intestinal toxins, and modulate nerve signaling - with emphasis on the vagus nerve. Additionally, gut dysbiosis results in impaired synthesis of signaling proteins affecting metabolic processes relevant to the development of Alzheimer's disease. Due to numerous links of gut microbiota to crucial metabolic and inflammatory pathways, attempts aimed at correcting the gut microflora composition may affect dementia pathology in a pleiotropic manner. Taking advantage of the metabolic effects of cold exposure on organisms by the introduction of whole-body cryostimulation in dementia patients could lead to alterations in gut microbiota and, therefore, decrease of an inflammatory response and insulin resistance, which remain one of the critical metabolic features of dementia. Further studies are needed in order to explore the potential application of recent findings and ways of achieving the desired goals.
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Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review.
Yan, J, Ouyang, J, Isnard, S, Zhou, X, Harypursat, V, Routy, JP, Chen, Y
Frontiers in immunology. 2021;:741658
Abstract
The intestinal microbiome is an essential so-called human "organ", vital for the induction of innate immunity, for metabolizing nutrients, and for maintenance of the structural integrity of the intestinal barrier. HIV infection adversely influences the richness and diversity of the intestinal microbiome, resulting in structural and functional impairment of the intestinal barrier and an increased intestinal permeability. Pathogens and metabolites may thus cross the "leaky" intestinal barrier and enter the systemic circulation, which is a significant factor accounting for the persistent underlying chronic inflammatory state present in people living with HIV (PLWH). Additionally, alcohol use and abuse has been found to be prevalent in PLWH and has been strongly associated with the incidence and progression of HIV/AIDS. Recently, converging evidence has indicated that the mechanism underlying this phenomenon is related to intestinal microbiome and barrier function through numerous pathways. Alcohol acts as a "partner" with HIV in disrupting microbiome ecology, and thus impairing of the intestinal barrier. Optimizing the microbiome and restoring the integrity of the intestinal barrier is likely to be an effective adjunctive therapeutic strategy for PLWH. We herein critically review the interplay among HIV, alcohol, and the gut barrier, thus setting the scene with regards to development of effective strategies to counteract the dysregulated gut microbiome and the reduction of microbial translocation and inflammation in PLWH.
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The importance of airway and lung microbiome in the critically ill.
Martin-Loeches, I, Dickson, R, Torres, A, Hanberger, H, Lipman, J, Antonelli, M, de Pascale, G, Bozza, F, Vincent, JL, Murthy, S, et al
Critical care (London, England). 2020;(1):537
Abstract
During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances.Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology.The body's resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity.In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.
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Review on the Alteration of Gut Microbiota: The Role of HIV Infection and Old Age.
Ashuro, AA, Lobie, TA, Ye, DQ, Leng, RX, Li, BZ, Pan, HF, Fan, YG
AIDS research and human retroviruses. 2020;(7):556-565
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Abstract
Human immunodeficiency virus (HIV) infection results in gut microbiota alteration and this is associated with immune activation and chronic inflammation. The gastrointestinal tract is a primary site of viral replication and thus HIV-induced loss of T-helper (Th) cells in the gut causes impairments in intestinal barriers, resulting in disruptions in intestinal immunity and precipitating into gut dysbiosis. Here, we show that late HIV diagnosis can negatively affect the immunological, virological, and clinical prognosis of the patients with its higher implication at an older age. Further, the review indicates that antiretroviral therapy affects the gut microbiota. We discussed the use of probiotics and prebiotics that have been indicated to play a promising role in reversing gut microbiota alteration in HIV patients. Though there are several studies reported with regard to such alterations in gut microbiota regarding HIV infection, there is a need to provide comprehensive updates. It is, therefore, the objective of this review to present most recently available evidence on the alteration of gut microbiota among HIV patients.
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The trace aminergic system: a gender-sensitive therapeutic target for IBS?
Pretorius, L, Smith, C
Journal of biomedical science. 2020;(1):95
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Abstract
Due to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a "missing link" that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.