Gut Microbiota Imbalance Research Articles

Plant Polyphenols Attenuate DSS-induced Ulcerative Colitis in Mice via Antioxidation, Anti-inflammation and Microbiota Regulation.

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.

Fructooligosaccharide (FOS) and Galactooligosaccharide (GOS) Improve Neuroinflammation and Cognition By Up-regulating IRS/PI3K/AKT Signaling Pathway in Diet-induced Obese Mice.

Increasing evidence has indicated that prebiotics as an alternative treatment for neuropsychiatric diseases. This study evaluated the prebiotics Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on the modulation of neuroinflammation and cognition in an experimental model of mice high-fat diet fed. Initially, mice were distributed in the following groups: (A) control standard diet (n = 15) and (B) HFD for 18 weeks (n = 30). In the 13th week, the mice were later divided into the following experimental groups: (A) Control (n = 15); (B) HFD (n = 14); and (C) HFD + Prebiotics (n = 14). From the 13th week, the HFD + Prebiotics group received a high-fat diet and a combination of FOS and GOS. In the 18th week, all animals performed the T-maze and Barnes Maze, and were later euthanized. Biochemical and molecular analyzes were performed to assess neuroinflammation, neurogenesis, synaptic plasticity, and intestinal inflammation. Mice fed HFD had higher blood glucose, triglyceridemia, cholesterolemia, and higher serum IL-1β associated with impaired learning and memory. These obese mice also showed activation of microglia and astrocytes and significant immunoreactivity of neuroinflammatory and apoptosis markers, such as TNF-α, COX-2, and Caspase-3, in addition to lower expression of neurogenesis and synaptic plasticity markers, such as NeuN, KI-67, CREB-p, and BDNF. FOS and GOS treatment significantly improved the biochemistry profile and decreased serum IL-1β levels. Treatment with FOS and GOS also reduced TNF-α, COX-2, Caspase-3, Iba-1, and GFAP-positive cells in the dentate gyrus, decreasing neuroinflammation and neuronal death caused by chronic HFD consumption. In addition, FOS and GOS promoted synaptic plasticity by increasing NeuN, p-CREB, BDNF, and KI-67, restoring spatial learning ability and memory. Moreover, FOS and GOS on HFD modulated the insulin pathway, which was proved by up-regulating IRS/PI3K/AKT signaling pathway, followed by a decreasing Aβ plate and Tau phosphorylation. Furthermore, the prebiotic intervention reshaped the HFD-induced imbalanced gut microbiota by modulating the composition of the bacterial community, markedly increasing Bacteroidetes. In addition, prebiotics decreased intestinal inflammation and leaky gut. In conclusion, FOS and GOS significantly modulated the gut microbiota and IRS/PI3K/AKT signaling pathway, decreased neuroinflammation, and promoted neuroplasticity improving spatial learning and memory. Schematic summarizing of the pathways by FOS and GOS improves memory and learning through the gut-brain axis. FOS and GOS improve the microbial profile, reducing intestinal inflammation and leaky gut in the distal colon. Specifically, the administration of FOS and GOS decreases the expression of TLR4, TNF-α, IL-1β, and MMP9 and increases the expression of occludin and IL-10. Prebiotics inhibit neuroinflammation, neuronal apoptosis, and reactive gliosis in the hippocampus but restore synaptic plasticity, neuronal proliferation, and neurogenesis.

Sanjin Paishi Decoction improves the imbalance of gut microbiota and regulates MAPK signaling pathway to inhibit calcium oxalate stones in rats.

Sanjin Paishi Decoction (SJPSD) has positive effects on stone prevention; however, there is a lack of convincing evidence in the prevention of calcium oxalate stones. This study aimed investigates the effect of SJPSD on calcium oxalate stones and to explore its mechanism. The rat model of calcium oxalate stones was established and rats were treated with different doses of SJPSD. The pathological damage of kidney tissues was observed by HE staining, the deposition of calcium oxalate crystals in kidney tissues was examined by Von Kossa staining, and the levels of creatinine (CREA), urea (UREA), calcium (Ca), phosphorus (P), and magnesium (Mg) in serum were analyzed biochemically, the levels of IL-1β, IL-6, and TNF-α in serum were measured by ELISA, and the protein expression of Raf1, MEK1, p-MEK1, ERK1/2, p-ERK1/2, and Cleaved caspase-3 in kidney tissues was analyzed by Western blot. Moreover, the changes in gut microbiota were analyzed by 16S rRNA sequencing. SJPSD attenuated the pathological damage of renal tissues, reduced the levels of CREA, UREA, Ca, P, and Mg, and inhibited the expression of Raf1, p-MEK1, p-ERK1/2, and Cleaved caspase-3 in renal tissues (P < 0.05). SJPSD treatment affected the composition of intestinal microbiota in rats with calcium oxalate stones. The mechanism of SJPSD inhibition of calcium oxalate stone injury in rats may be related to the inhibition of the MAPK signaling pathway and regulation of gut microbiota imbalance.

Understanding the gut microbiota in cancer cachexia.

Cachexia is a complex, multifactorial syndrome primarily characterized by weight loss, muscle wasting, anorexia, and systemic inflammation. It is prevalent in cancer patients and is associated with a poor prognosis, including lower resistance to intervention toxicity, quality of life, and survival, compared to patients without the syndrome. The gut microbiota and its metabolites have been shown to influence host metabolism and immune response. Our article reviews the current evidence suggesting a role of gut microbiota in the development and progression of cachexia, while discussing the potential mechanisms involved. We also describe promising interventions targeting gut microbiota aiming to improve outcomes related to cachexia. Dysbiosis, an imbalance in gut microbiota, has been associated with cancer cachexia through pathways involving muscle wasting, inflammation, and gut barrier dysfunction. Interventions targeting gut microbiota, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have shown promising results in managing this syndrome in animal models. However, evidence in humans is currently limited. Mechanisms linking gut microbiota and cancer cachexia need to be further explored, and additional human research is necessary to evaluate the appropriate dosages, safety, and long-term outcomes of prebiotic and probiotic use in microbiota management for cancer cachexia.

Gut Microbiota and Antibiotic Treatments for the Main Non-Oncologic Hepato-Biliary-Pancreatic Disorders.

The gut microbiota is a pivotal actor in the maintenance of the balance in the complex interconnections of hepato-biliary-pancreatic system. It has both metabolic and immunologic functions, with an influence on the homeostasis of the whole organism and on the pathogenesis of a wide range of diseases, from non-neoplastic ones to tumorigenesis. The continuous bidirectional metabolic communication between gut and hepato-pancreatic district, through bile ducts and portal vein, leads to a continuous interaction with translocated bacteria and their products. Chronic liver disease and pancreatic disorders can lead to reduced intestinal motility, decreased bile acid synthesis and intestinal immune dysfunction, determining a compositional and functional imbalance in gut microbiota (dysbiosis), with potentially harmful consequences on the host's health. The modulation of the gut microbiota by antibiotics represents a pioneering challenge with striking future therapeutic opportunities, even in non-infectious diseases. In this setting, antibiotics are aimed at harmonizing gut microbial function and, sometimes, composition. A more targeted and specific approach should be the goal to pursue in the future, tailoring the treatment according to the type of microbiota modulation to be achieved and using combined strategies.

Lactobacillus acidophilus and propionate attenuate Sjögren’s syndrome by modulating the STIM1-STING signaling pathway

BackgroundSjögren’s syndrome (SS) is an autoimmune disease characterized by inflammation of the exocrine gland. An imbalance of gut microbiota has been linked to SS. However, the molecular mechanism is unclear. We investigated the effects of Lactobacillus acidophilus (L. acidophilus) and propionate on the development and progression of SS in mouse model.MethodsWe compared the gut microbiomes of young and old mice. We administered L. acidophilus and propionate up to 24 weeks. The saliva flow rate and the histopathology of the salivary glands were investigated, and the effects of propionate on the STIM1-STING signaling pathway were evaluated in vitro.ResultsLactobacillaceae and Lactobacillus were decreased in aged mice. SS symptoms were ameliorated by L. acidophilus. The abundance of propionate-producing bacterial was increased by L. acidophilus. Propionate ameliorated the development and progression of SS by inhibiting the STIM1-STING signaling pathway.ConclusionsThe findings suggest that Lactobacillus acidophilus and propionate have therapeutic potential for SS.8VNBPUvEwXTTUuuFm3yGCMVideo

Cross talk between Paneth and tuft cells drives dysbiosis and inflammation in the gut mucosa

Gut microbiota imbalance (dysbiosis) is increasingly associated with pathological conditions, both within and outside the gastrointestinal tract. Intestinal Paneth cells are considered to be guardians of the gut microbiota, but the events linking Paneth cell dysfunction with dysbiosis remain unclear. We report a three-step mechanism for dysbiosis initiation. Initial alterations in Paneth cells, as frequently observed in obese and inflammatorybowel diseases patients, cause a mild remodeling of microbiota, with amplification of succinate-producing species. SucnR1-dependent activation of epithelial tuft cells triggers a type 2 immune response that, in turn, aggravates the Paneth cell defaults, promoting dysbiosis and chronic inflammation. We thus reveal a function of tuft cells in promoting dysbiosis following Paneth cell deficiency and an unappreciated essential role of Paneth cells in maintaining a balanced microbiota to prevent inappropriate activation of tuft cells and deleterious dysbiosis. This succinate-tuft cell inflammation circuit may also contribute to the chronic dysbiosis observed in patients.

Harnessing the potential of probiotics in the treatment of alcoholic liver disorders.

In the current scenario, prolonged consumption of alcohol across the globe is upsurging an appreciable number of patients with the risk of alcohol-associated liver diseases. According to the recent report, the gut-liver axis is crucial in the progression of alcohol-induced liver diseases, including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Despite several factors associated with alcoholic liver diseases, the complexity of the gut microflora and its great interaction with the liver have become a fascinating area for researchers due to the high exposure of the liver to free radicals, bacterial endotoxins, lipopolysaccharides, inflammatory markers, etc. Undoubtedly, alcohol-induced gut microbiota imbalance stimulates dysbiosis, disrupts the intestinal barrier function, and trigger immune as well as inflammatory responses which further aggravate hepatic injury. Since currently available drugs to mitigate liver disorders have significant side effects, hence, probiotics have been widely researched to alleviate alcohol-associated liver diseases and to improve liver health. A broad range of probiotic bacteria like Lactobacillus, Bifidobacteria, Escherichia coli, Sacchromyces, and Lactococcus are used to reduce or halt the progression of alcohol-associated liver diseases. Several underlying mechanisms, including alteration of the gut microbiome, modulation of intestinal barrier function and immune response, reduction in the level of endotoxins, and bacterial translocation, have been implicated through which probiotics can effectively suppress the occurrence of alcohol-induced liver disorders. This review addresses the therapeutic applications of probiotics in the treatment of alcohol-associated liver diseases. Novel insights into the mechanisms by which probiotics prevent alcohol-associated liver diseases have also been elaborated.

Dysbiosis and Alzheimer's disease: role of probiotics, prebiotics and synbiotics.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia and the accumulation of amyloid beta in the brain. Recently, microbial dysbiosis has been identified as one of the major factors involved in the onset and progression of AD. Imbalance in gut microbiota is known to affect central nervous system (CNS) functions through the gut-brain axis and involves inflammatory, immune, neuroendocrine and metabolic pathways. An altered gut microbiome is known to affect the gut and BBB permeability, resulting in imbalance in levels of neurotransmitters and neuroactive peptides/factors. Restoration of levels of beneficial microorganisms in the gut has demonstrated promising effects in AD in pre-clinical and clinical studies. The current review enlists the important beneficial microbial species present in the gut, the effect of their metabolites on CNS, mechanisms involved in dysbiosis related to AD and the beneficial effects of probiotics on AD. It also highlights challenges involved in large-scale manufacturing and quality control of probiotic formulations.

Astragaloside IV ameliorate acute alcohol-induced liver injury in mice via modulating gut microbiota and regulating NLRP3/caspase-1 signaling pathway

Purpose Astragaloside IV (AS-IV) is a natural saponin substance extracted from the plant Radix Astragali with anti-inflammatory, antioxidant, anti-apoptotic, and liver-protecting effects. This study was to evaluate the liver protection effect of AS-IV on mice after acute alcohol stimulation. Materials and Methods Mice were orally administrated with AS-IV (50, 150, and 500 mg/kg, respectively), and sodium carboxymethyl cellulose (CMC, 50 mg/kg) daily for 7 days, before giving five alcohol-intragastric injections. Results Results suggested that the levels of serum ALT and AST, liver SOD, GSH-PX, 4-HNE, and MDA, serum and liver TNF-α, IL-1β, and IL-6, serum lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), diamine oxidase (DAO) and Myeloperoxidase (MPO), the mRNA and protein expression of hepatic NLRP3, Caspase-1, IL-1β, and IL-18 were significantly decreased in AS-IV-treated mice compared with the model group. Moreover, the effect of AS-IV on histopathology of liver tissue confirmed its protective function. Furthermore, AS-IV ameliorated the gut microbiota imbalance and adjusted the abundance of the following dysfunctional bacteria closer to the control group: Butyricicoccus, Turicibacter, Akkermansia, Anaerotruncus, and Mucispirillum. A strong correlation between intestinal bacteria and potential biomarkers was found. Conclusion Together, our findings indicated that AS-IV exert the hepatoprotective effect by modulating the gut microbiota imbalance and regulating NLRP3/Caspase-1 signaling pathway.

Development of Centella asiatica beverages with potential antioxidant and prebiotic activity for maintaining intestinal health

Herbal beverages with antioxidant and prebiotic properties are promising nutraceutical candidates to prevent or cure various intestinal diseases that involve oxidative stress and/or imbalance of gut microbiota. In this study, partial chemical characterization of the small molecule (ethanol soluble) and polymeric (ethanol precipitated and TCA precipitated) fractions of two types of beverages (Centella asiatica beverages; decoction and infusion) from Centella asiatica were investigated. Fifty-two compounds with known record of antioxidant or anti-inflammation effect were identified in both beverages. All targeted fractions of two beverages had reducing capacity and free radical scavenging ability. The in vitro antioxidant capacity of both beverages and their individual fractions was further confirmed in H2O2 stressed Saccharomyces cerevisea models. However, the lipid peroxidation lessening ability was only observed in the small molecule fractions. The results suggested that different types of molecules in beverages can succeed via multiple mechanisms to reverse the oxidative stress in cells. In a separate experiment, both beverages could significantly retard the growth of the gastrointestinal pathogen Bacillus cereus. On the other hand, the CABs promoted growth of a well-known probiotic strain Lacticaseibacillus rhamnosus ATCC 53103 when tested individually as well as when grown together with Bacillus cereus. This study suggests that the beverages may balance antioxidant status as well as maintain quantity and diversity of microbiota to protect intestinal health. Additionally, a framework has been put forward to highlight the possible sites of intestine where an herbal beverage can act to prevent and cure some of the intestinal diseases.

SIRT2 Deficiency Aggravates Diet-Induced Nonalcoholic Fatty Liver Disease through Modulating Gut Microbiota and Metabolites.

Non-alcoholic fatty liver disease (NAFLD), characterized by excessive lipid accumulation in hepatocytes, is an increasing global healthcare burden. Sirtuin 2 (SIRT2) functions as a preventive molecule for NAFLD with incompletely clarified regulatory mechanisms. Metabolic changes and gut microbiota imbalance are critical to the pathogenesis of NAFLD. However, their association with SIRT2 in NAFLD progression is still unknown. Here, we report that SIRT2 knockout (KO) mice are susceptible to HFCS (high-fat/high-cholesterol/high-sucrose)-induced obesity and hepatic steatosis accompanied with an aggravated metabolic profile, which indicates SIRT2 deficiency promotes NAFLD-NASH (nonalcoholic steatohepatitis) progression. Under palmitic acid (PA), cholesterol (CHO), and high glucose (Glu) conditions, SIRT2 deficiency promotes lipid deposition and inflammation in cultured cells. Mechanically, SIRT2 deficiency induces serum metabolites alteration including upregulation of L-proline and downregulation of phosphatidylcholines (PC), lysophosphatidylcholine (LPC), and epinephrine. Furthermore, SIRT2 deficiency promotes gut microbiota dysbiosis. The microbiota composition clustered distinctly in SIRT2 KO mice with decreased Bacteroides and Eubacterium, and increased Acetatifactor. In clinical patients, SIRT2 is downregulated in the NALFD patients compared with healthy controls, and is associated with exacerbated progression of normal liver status to NAFLD to NASH in clinical patients. In conclusion, SIRT2 deficiency accelerates HFCS-induced NAFLD-NASH progression by inducing alteration of gut microbiota and changes of metabolites.

Anti-diabetic effect of modified ‘Guanximiyou’ pummelo peel pectin on type 2 diabetic mice via gut microbiota

This study aimed to investigate the mechanisms of nature and modified ‘Guanximiyou’ pummelo peel pectin (GGP and MGGP) in alleviating T2DM through in vitro and in vivo. After modification, pectin was transformed from high methoxy pectin (HMP) to low methoxy pectin (LMP), and the content of galacturonic acid was increased. These made MGGP have stronger antioxidant capacity and better inhibition effect on corn starch digestion in vitro. In vivo experiments have shown that both GGP and MGGP inhibited the development of diabetes after 4 weeks of ingestion. However, MGGP can more effectively reduce blood glucose and regulate lipid metabolism, and has significant antioxidant capacity and the ability to promote SCFAs secretion. In addition, 16S rRNA analysis showed that MGGP changed the composition of intestinal microbiota in diabetic mice, decreased the abundance of Proteobacteria, and increased the relative abundance of Akkermansia, Lactobacillus, Oscillospirales and Ruminococcaceae. The phenotypes of the gut microbiome also changed accordingly, indicating that MGGP can inhibit the growth of pathogenic bacteria, alleviate intestinal functional metabolic disorders and reverse the potential risk of related complications. Altogether, our findings demonstrate that MGGP, as a dietary polysaccharide, may inhibit the development of diabetes by reversing the imbalance of gut microbiota.

Brief pup separation during lactation confers resilience in behavioural deficits induced by chronic restraint stress in postpartum C57BL/6J dams.

The postpartum period is a complex time for females that affects health recovery. Stress during this period is one of the main risk factors for depression. Therefore, preventing stress-induced depression in the postpartum period is of great importance. Pup separation (PS) is a natural paradigm of postpartum care; however, the effect of different PS protocols during lactation on stress-induced depressive behaviours in dams is unknown. Lactating C57BL/6J mice were subjected to no pup separation (NPS), brief PS (15 min/day, PS15) or long PS (180 min/day, PS180) from postpartum day 1 to postpartum day 21 and were then subjected to chronic restraint stress (CRS) for 21 days. Behavioural tests, specifically the open field test (OFT), elevated plus maze (EPM) test and tail suspension test (TST), were performed. The expression of mRNA and protein in the hippocampus and microbiota composition were also assessed. We observed CRS-induced anxiety- and depression-like behaviours in NPS dams. In addition, in NPS dams, microglial activation and the levels of NOD-like receptor pyrin domain containing 3, caspase-1 and interleukin-1β were increased, whereas expression levels of collapsing response mediator protein 2 (CRMP2) and α-tubulin were decreased. However, immobility time in the TST was lower in PS15+CRS dams than in NPS+CRS dams, and time spent in the centre during the OFT and in the open arms during the EPM test was higher in PS15+CRS dams, indicating resilience. Expression of hippocampal biomarkers of neuroinflammation was inhibited and levels of CRMP2-mediated neuroplasticity were increased in PS15+CRS dams. Notably, we observed taxonomic changes in the cecal microbiota across different PS groups, as well as relationships between gut microbiota composition and some biomarkers of hippocampal neuroinflammation and neuroplasticity. The sample size for gut microbiota analysis in this study was small. Collectively, the results of this study confirm that brief PS confers stress resilience in CRS-induced behavioural deficits and reverses hippocampal neuroinflammation-neuroplasticity injury and gut microbiota imbalance.

Gut microbiota dysbiosis in rats with LPS-induced liver diseases affected by Aronia melanocarpa polyphenols

It is well known that there is an imbalance of gut microbiota in liver diseases, our previous study has proved that Aronia melanocarpa polyphenols (AMPs) can modulate the gut microbiota and affect the progression of liver diseases. Here, we analyzed the gut microbiota by 16S rRNA sequencing and bioinformatic analysis to explored the changes of gut microbiota composition and functions after LPS and AMPs intervention. Our results showed that there were significant differences in the gut microbiota structure between different treatment groups, such as increasing the abundance of Lactobacillaceae and Muribaculaceae, decreasing the abundance of Ruminococcaceae and Acidaminococcaceae. Furthermore, PICRUSt prediction showed that 29 functional pathways have changed significantly which may promote the treatment of liver diseases. This study could help to supplement the information about the community of gut microbiota in liver diseases and provide a new strategy for the treatment of liver diseases.

Gut microbiota in perioperative neurocognitive disorders: current evidence and future directions.

Perioperative neurocognitive disorders (PND) is a common surgical anesthesia complication characterized by impairment of memory, attention, language understanding and social ability, which can lead to a decline in the quality of life of patients, prolong the hospitalization period and increase the mortality rate. PND has a high incidence rate, which has a great impact on postoperative recovery and quality of life of patients, and has caused a heavy economic burden to society and families. In recent years, PND has become an important public health problem. The high risk population of PND is more prone to gut microbiota imbalance, and gut microbiota may also affect the inflammatory response of the central nervous system through the microbiota-gut-brain axis. Meanwhile, Neuroinflammation and immune activation are important mechanisms of PND. Regulating gut microbiota through probiotics or fecal bacteria transplantation can significantly reduce neuroinflammation, reduce the abnormal activation of immune system and prevent the occurrence of PND. This review summarizes the research progress of gut microbiota and PND, providing basis for the prevention and treatment of PND.

The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals' susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.

Probiotics for Neurodegenerative Diseases: A Systemic Review.

Neurodegenerative disorders (ND) are a group of conditions that affect the neurons in the brain and spinal cord, leading to their degeneration and eventually causing the loss of function in the affected areas. These disorders can be caused by a range of factors, including genetics, environmental factors, and lifestyle choices. Major pathological signs of these diseases are protein misfolding, proteosomal dysfunction, aggregation, inadequate degradation, oxidative stress, free radical formation, mitochondrial dysfunctions, impaired bioenergetics, DNA damage, fragmentation of Golgi apparatus neurons, disruption of axonal transport, dysfunction of neurotrophins (NTFs), neuroinflammatory or neuroimmune processes, and neurohumoral symptoms. According to recent studies, defects or imbalances in gut microbiota can directly lead to neurological disorders through the gut-brain axis. Probiotics in ND are recommended to prevent cognitive dysfunction, which is a major symptom of these diseases. Many in vivo and clinical trials have revealed that probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei, etc.) are effective candidates against the progression of ND. It has been proven that the inflammatory process and oxidative stress can be modulated by modifying the gut microbiota with the help of probiotics. As a result, this study provides an overview of the available data, bacterial variety, gut-brain axis defects, and probiotics' mode of action in averting ND. A literature search on particular sites, including PubMed, Nature, and Springer Link, has identified articles that might be pertinent to this subject. The search contains the following few groups of terms: (1) Neurodegenerative disorders and Probiotics OR (2) Probiotics and Neurodegenerative disorders. The outcomes of this study aid in elucidating the relationship between the effects of probiotics on different neurodegenerative disorders. This systematic review will assist in discovering new treatments in the future, as probiotics are generally safe and cause mild side effects in some cases in the human body.

Microbiota-gut-brain axis and related therapeutics in Alzheimer's disease: prospects for multitherapy and inflammation control.

Alzheimer's disease (AD) is the most common type of dementia in the elderly and causes neurodegeneration, leading to memory loss, behavioral disorder, and psychiatric impairment. One potential mechanism contributing to the pathogenesis of AD may be the imbalance in gut microbiota, local and systemic inflammation, and dysregulation of the microbiota-gut-brain axis (MGBA). Most of the AD drugs approved for clinical use today are symptomatic treatments that do notimprove AD pathologic changes. As a result, researchers are exploring novel therapeutic modalities. Treatments involving the MGBA include antibiotics, probiotics, transplantation of fecal microbiota, botanical products, and others. However, single-treatment modalities are not as effective as expected, and a combination therapy is gaining momentum. The purpose ofthis review is to summarize recent advances in MGBA-related pathological mechanisms and treatment modalities in AD and to propose a new concept of combination therapy. "MGBA-based multitherapy" is an emerging view of treatment in which classic symptomatic treatments and MGBA-based therapeutic modalities are used in combination. Donepezil and memantine are two commonly used drugs in AD treatment. On the basis of the single/combined use of these two drugs, two/more additional drugs and treatment modalities that target the MGBA are chosen based on the characteristics of the patient's condition as an adjuvant treatment, as well as the maintenance of good lifestyle habits. "MGBA-based multitherapy" offers new insights for the treatment of cognitive impairment in AD patients and is expected to show good therapeutic results.

Glaucocalyxin A attenuates carbon tetrachloride-induced liver fibrosis and improves the associated gut microbiota imbalance.

Liver fibrosis refers to the pathophysiological process of dysplasia on the connective tissue of the liver, caused by a variety of pathogenic factors. Glaucocalyxin A (GLA) has anticoagulation, antibacterial, anti-inflammation, antioxidant and antitumour properties. However, whether GLA ameliorates liver fibrosis or not is still unclear. In this study, a liver fibrosis model was established using male C57BL/6 mice. The mice were treated with 5 and 10 mg/kg GLA via intraperitoneal injection, respectively. The ones that were treated with 5 mg/kg OCA were used as the positive control group. The levels of liver function, liver fibrosis biomarkers and liver pathological changes were then evaluated. We also explored the effects of GLA on inflammatory response and liver cell apoptosis. In addition, we investigated the gut microbiota mechanisms of GLA on liver fibrosis. The results from this study that GLA could significantly decrease the level of liver function (AST, ALT, TBA) and liver fibrosis (HA, LN, PC-III, IV-C). On the other hand, a significant decrease in inflammation levels (IL-1β, TNF-α) were also noted. GLA also improves CCl4-induced pathological liver injuries and collagen deposition, in addition to decreasing apoptosis levels. In addition, an increase in the ratio of Bacteroidetes and Firmicutes in liver disease was also observed. GLA also improves the gut microbiota. In conclusion, GLA attenuates CCl4-induced liver fibrosis and improves the associated gut microbiota imbalance.