Disorders Axis Research Articles

Ginsenoside Rh4 remodels the periphery microenvironment by targeting the brain-gut axis to alleviate depression-like behaviors

Depression is a neuropsychiatric disease that threatens the physical and mental health of humans worldwide. This study explored the potential anti-depressant effects of ginsenoside Rh4 and its mechanisms of action. The results showed that Rh4 could significantly inhibit depression-like behavior in the depression mouse model and alleviate neuronal damage and hypothalamic–pituitary–adrenal axis disorder. Concurrently, Rh4 inhibits hippocampal neuronal apoptosis and synaptic structural damage due to the overexpression of proinflammatory cytokines and overactivation of microglia and astrocytes by inhibiting the immune-inflammatory response and signaling molecular interaction pathways. Rh4 can also improve intestinal flora and increase the short-chain fatty-acids content. The correlation analysis indicated that the Rh4-inhibited LPS/NLRP3/caspase-1/IL-1β signaling pathway plays a key role in ameliorating depression. Therefore, this study provides valuable insights into the mode of action of Rh4 on the brain-gut axis in depression, suggesting that Rh4 may be a promising clinical drug for the treatment of depression.

Protective role of the dandelion extract against the blood-liver axis, cell membranes, and anemia disorder in sodium benzoate-exposed rats.

Sodium benzoate(SB) as an additive in various food products prevents the growth of microbes. Although SB is considered safe, many studies have reported adverse effects. The aim of this study was to investigate the effect of dandelion extract on cell damage and hematologicaland biochemical disorders induced by SB in male albino rats. Different doses of SB (200 and 600 mg/kg) and ethanolic dandelion root extract (D) (40 mg/kg) were used in a 2-week treatment of rats. Rat mortality and a higher frequency of behavioral alterations such as apathy, anxiety, and aggression have been reported at a higher dose of SB. Changes in urine pH, proteinuria, nitrituria, and bilirubinemia caused by SB were regulated by adding dandelion extract. Analysis of specific serum and urine parameters, as well as microscopic analysis of hepatocytes, showed liver and kidney failure. Anemia associated with hemolytic disorder due to erythrocyte impairedthe presence of acanthocytes, and decreased values of erythrocyte blood count, hemoglobin concentration, average red blood cell size, hemoglobin amount per red blood cell, and mean corpuscular hemoglobin concentration were caused by SB treatment. As a dietary supplement, dandelion extract can be useful in the preventionof SB-induced liver and kidney injury, and also a remedy against induced anemia, neutropenia, thrombocytopenia, hyperproteinemia, hyperglycemia, and reduction of inflammatory responses.

Sodium-glucose cotransporter 2 inhibitor ameliorates high fat diet-induced hypothalamic-pituitary-ovarian axis disorders.

High-fat diet (HFD) consumption is known to be associated with ovulatory disorders among women of reproductive age. Previous studies in animal models suggest that HFD-induced microglia activation contributes to hypothalamic inflammation. This causes the dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis, leading to subfertility. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of lipid-soluble antidiabetic drugs that target primarily the early proximal tubules in kidney. Recent evidence revealed an additional expression site of SGLT2 in the central nervous system (CNS), indicating a promising role of SGLT2 inhibitors in the CNS. In type 2 diabetes patients and rodent models, SGLT2 inhibitors exhibit neuroprotective properties through reduction of oxidative stress, alleviation of cerebral atherosclerosis and suppression of microglia-induced neuroinflammation. Furthermore, clinical observations in patients with polycystic ovary syndrome (PCOS) demonstrated that SGLT2 inhibitors ameliorated patient anthropometric parameters, body composition and insulin resistance. Therefore, it is of importance to explore the central mechanism of SGLT2 inhibitors in the recovery of reproductive function in patients with PCOS and obesity. Here, we review the hypothalamic inflammatory mechanisms of HFD-induced microglial activation, with a focus on the clinical utility and possible mechanism of SGLT2 inhibitors in promoting reproductive fitness.

Down-regulating Interleukin-22/Interleukin-22 binding protein axis promotes inflammation and aggravates diet-induced metabolic disorders

The prevalence of metabolic diseases has become a severe public health problem. Previously, we reported that Interleukin-22 (IL-22) was independently associated with type 2 diabetes mellitus and cardiovascular disease, and could protect endothelial cells from glucose- and lysophosphatidylcholine-induced injury. The activity of IL-22 is strongly regulated by IL-22-binding protein (IL-22BP). The aim of this investigation was to determine the effect of IL-22/IL-22BP axis on glucolipid metabolism. Serum IL-22 and IL-22BP expression in metabolic syndrome (MetS) patients and healthy controls was examined. IL-22BP-knockout (IL-22ra2−/−) and wild-type (WT) mice were fed with control diet (CTD) and high-fat diet (HFD) for 12 weeks. The IL-22 related pathway expression, the glucolipid metabolism, and inflammatory markers in mice were examined. Serum IL-22 and IL-22BP levels were found significantly increased in MetS patients (p < 0.001). IL-22BP deficiency down-regulated IL-22-related pathway, aggravated glucolipid metabolism disorder, and promoted inflammation in mice. Collectively, this work deepens the understanding of the relationship between IL-22/IL-22BP axis and metabolism disorders, and identified that down-regulation of IL-22/IL-22BP axis promotes metabolic disorders in mice.

Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Prevention of dementia is a public health priority, and the identification of potential biomarkers may provide benefits for early detection and prevention. This study investigates the association of common serum laboratory tests with the risk of incident dementia. Among 407,190 participants from the UK Biobank (median follow-up of 9.19 years), we investigated the linear and nonlinear effects of 30 laboratory measures on the risk of all-cause dementia using Cox models and restricted cubic spline models. We found that dementia incidence was associated with low vitamin D concentration (hazard ratio 0.994, 95% confidence interval 0.993–0.996), indicators of endocrine disorders: IGF-1 level (P for non-linearity = 1.1E-05), testosterone level (P for non-linearity = 0.006); high sex-hormone-binding globulin level (HR 1.004, 95% CI: 1.003–1.006); reduced liver function: lower alanine aminotransferase (HR 0.990, 95% CI: 0.986–0.995); renal dysfunction: cystatin C level (P for non-linearity = 0.028); oxidative stress: lower urate level (HR 0.998, 95% CI: 0.998–0.999); lipids dysregulation: lower LDL (HR 0.918, 95% CI: 0.872–0.965) and triglycerides (HR 0.924, 95% CI: 0.882–0.967) concentrations; insulin resistance: high glucose (HR 1.093, 95% CI: 1.045–1.143) and HbA1c (HR 1.017, 95% CI: 1.009–1.025) levels; immune dysbiosis: C−reactive protein (P for non-linearity = 5.5E-09). In conclusion, markers of vitamin D deficiency, GH-IGF-1 axis disorders, bioactive sex hormone deficiency, reduced liver function, renal abnormalities, oxidation, insulin resistance, immune dysbiosis, and lipids dysregulation were associated with incident dementia. Our results support a contributory role of systemic disorders and diverse biological processes to onset of dementia.

The molecular signaling of exercise and obesity in the microbiota-gut-brain axis.

Obesity is one of the major pandemics of the 21st century. Due to its multifactorial etiology, its treatment requires several actions, including dietary intervention and physical exercise. Excessive fat accumulation leads to several health problems involving alteration in the gut-microbiota-brain axis. This axis is characterized by multiple biological systems generating a network that allows bidirectional communication between intestinal bacteria and brain. This mutual communication maintains the homeostasis of the gastrointestinal, central nervous and microbial systems of animals. Moreover, this axis involves inflammatory, neural, and endocrine mechanisms, contributes to obesity pathogenesis. The axis also acts in appetite and satiety control and synthesizing hormones that participate in gastrointestinal functions. Exercise is a nonpharmacologic agent commonly used to prevent and treat obesity and other chronic degenerative diseases. Besides increasing energy expenditure, exercise induces the synthesis and liberation of several muscle-derived myokines and neuroendocrine peptides such as neuropeptide Y, peptide YY, ghrelin, and leptin, which act directly on the gut-microbiota-brain axis. Thus, exercise may serve as a rebalancing agent of the gut-microbiota-brain axis under the stimulus of chronic low-grade inflammation induced by obesity. So far, there is little evidence of modification of the gut-brain axis as a whole, and this narrative review aims to address the molecular pathways through which exercise may act in the context of disorders of the gut-brain axis due to obesity.

Prevalence of gastrointestinal disorders in individuals with RASopathies: May RAS/MAP/ERK pathway dysfunctions be a model of neuropathic pain and visceral hypersensitivity?

RASopathies are a group of neurodevelopmental syndromes caused by germline variants in genes of the Ras/MAP/ERK pathway. Growth failure, neurological involvement, and pain represent the main features of these conditions. ERK signaling cascade plays a crucial role in nociception and visceral pain and it is likely implicated in the genesis of neuropathic pain and maintenance of altered pain states. We studied the prevalence of abdominal pain and functional gastrointestinal (GI) disorders in a large sample of individuals with RASopathies. A brief pain inventory questionnaire and semi-structured dedicated interview were used to investigate presence and localization of pain. A Rome IV questionnaire was used to screen for functional GI disorders. Eighty patients with clinical and molecular diagnoses of RASopathy were recruited (42 with Noonan syndrome; 17 with Costello Syndrome and 21 with cardio-facio-cutaneous syndrome). Overall, the prevalence of abdominal pain was 44% and prevalence of functional GI disorders was 78% with constipation, abdominal pain, and aerophagia being the most frequently detected ones. A significant association was found between pain and irritable bowel syndrome, functional constipation and aerophagia. Children with RASopathies have a high prevalence of functional gastrointestinal disorders. These children could represent a good in vivo model to study neuropathic pain, visceral hypersensitivity and gut-brain axis disorders.

Osteotomies and Total Knee Arthroplasty: Systematic Review and Meta-Analysis.

Total knee replacement (TKA) is a frequent modality performed in patients with osteoarthritis. Specific circumstances can make it much more difficult to execute successfully, and additional procedures such as osteotomy may be required. The aim of this study was to perform a meta-analysis and systematic review of osteotomies combined with TKA. Methods: In June 2022, a search PubMed, Embase, Cochrane, and Clinicaltrials was undertaken, adhering to PRISMA guidelines. The search included the terms “osteotomy” and “total knee arthroplasty”. Results: Two subgroups (tibial tubercle osteotomy and medial femoral condyle osteotomy) were included in the meta-analysis. Further subgroups were described as a narrative review. The primary outcome showed no significant difference in favor to TTO. Secondary outcomes showed improved results in all presented subgroups compared to preoperative status. Conclusion: This study showed a significant deficit of randomized control trials treated with osteotomies, in addition to TKA, and a lack of evidence-based surgical guidelines for the treatment of patients with OA in special conditions: posttraumatic deformities, stiff knee, severe varus, and valgus axis or patella disorders.

The influence of insulin and diabetes mellitus on male reproductive health

Diabetes mellitus affects the function of the male reproductive system through glucose metabolism and endocrine influences of insulin. Glucose metabolism is an important event in spermatogenesis and the maintenance of the activity of specific functions of motility and the ability of spermatozoa to fertilize, and metabolic disorders are caused by absolute or relative insulin deficiency and insulin resistance, which leads to the degradation of male reproduction. Inadequate effects of insulin are aimed at changing the morphological and functional characteristics of the seed material, the physiological state of the hypothalamic-pituitary-gonadal axis, testicular function, testosterone synthesis and spermatogenesis disorders. Thus, this article elucidates the impact of diabetes on spermatogenesis and some insulin-dependent mechanisms on male fertility.

Research progress on the relationship between gut-liver axis disorder and sepsis

Sepsis is a life-threatening organ dysfunction caused by an uncontrolled host response to infection. The mechanism of sepsis is extremely complicated and the mortality is still high. Persistent researches provide an important way to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. In recent years, more and more studies have shown that gut-liver axis disorders, especially those caused by intestinal dysbiosis, intestinal barrier dysfunction, abnormal liver immune function, and bile acid metabolism disorders, play an important role in the occurrence and development of sepsis. This review describes the research progress of gut-liver axis disorders in the pathogenesis of sepsis for providing new ideas for clinical treatment.

The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Application of zebrafish in the study of the gut microbiome.

Zebrafish (Danio rerio) have attracted much attention over the past decade as a reliable model for gut microbiome research. Owing to their low cost, strong genetic and development coherence, efficient preparation of germ‐free (GF) larvae, availability in high‐throughput chemical screening, and fitness for intravital imaging in vivo, zebrafish have been extensively used to investigate microbiome‐host interactions and evaluate the toxicity of environmental pollutants. In this review, the advantages and disadvantages of zebrafish for studying the role of the gut microbiome compared with warm‐blooded animal models are first summarized. Then, the roles of zebrafish gut microbiome on host development, metabolic pathways, gut‐brain axis, and immune disorders and responses are addressed. Furthermore, their applications for the toxicological assessment of aquatic environmental pollutants and exploration of the molecular mechanism of pathogen infections are reviewed. We highlight the great potential of the zebrafish model for developing probiotics for xenobiotic detoxification, resistance against bacterial infection, and disease prevention and cure. Overall, the zebrafish model promises a brighter future for gut microbiome research.

The Good, the Bad, and the Ugly-Chances, Challenges, and Clinical Implications of Avoidance Research in Psychosomatic Medicine.

Avoidance behaviors are shaped by associative learning processes in response to fear of impending threats, particularly physical harm. As part of a defensive repertoire, avoidance is highly adaptive in case of acute danger, serving a potent protective function. However, persistent or excessive fear and maladaptive avoidance are considered key factors in the etiology and pathophysiology of anxiety- and stress-related psychosomatic disorders. In these overlapping conditions, avoidance can increase the risk of mental comorbidities and interfere with the efficacy of cognitive behavioral treatment approaches built on fear extinction. Despite resurging interest in avoidance research also in the context of psychosomatic medicine, especially in conditions associated with pain, disturbed interoception, and disorders of the gut-brain axis, current study designs and their translation into the clinical context face significant challenges limiting both, the investigation of mechanisms involved in avoidance and the development of novel targeted treatment options. We herein selectively review the conceptual framework of learning and memory processes, emphasizing how classical and operant conditioning, fear extinction, and return of fear shape avoidance behaviors. We further discuss pathological avoidance and safety behaviors as hallmark features in psychosomatic diseases, with a focus on anxiety- and stress-related disorders. Aiming to emphasize chances of improved translational knowledge across clinical conditions, we further point out limitations in current experimental avoidance research. Based on these considerations, we propose means to improve existing avoidance paradigms to broaden our understanding of underlying mechanisms, moderators and mediators of avoidance, and to inspire tailored treatments for patients suffering from psychosomatic disorders.

Mouse Cre drivers: tools for studying disorders of the human female neuroendocrine-reproductive axis†.

Benign disorders of the human female reproductive system, such primary ovarian insufficiency and polycystic ovary syndrome are associated with infertility and recurrent miscarriage, as well as increased risk of adverse health outcomes, including cardiovascular disease and type 2 diabetes. For many of these conditions, the contributing molecular and cellular processes are poorly understood. The overarching similarities between mice and humans have rendered mouse models irreplaceable in understanding normal physiology and elucidating pathological processes that underlie disorders of the female reproductive system. The utilization of Cre-LoxP recombination technology, which allows for spatial and temporal control of gene expression, has identified the role of numerous genes in development of the female reproductive system and in processes, such as ovulation and endometrial decidualization, that are required for the establishment and maintenance of pregnancy in mammals. In this comprehensive review, we provide a detailed overview of Cre drivers with activity in the neuroendocrine-reproductive axis that have been used to study disruptions in key intracellular signaling pathways. We first summarize normal development of the hypothalamus, pituitary, ovary, and uterus, highlighting similarities and differences between mice and humans. We then describe human conditions resulting from abnormal development and/or function of the organ. Finally, we describe loss-of-function models for each Cre driver that elegantly recapitulate some key features of the human condition and are associated with impaired fertility. The examples we provide illustrate use of each Cre driver as a tool for elucidating genetic and molecular underpinnings of reproductive dysfunction.

Convergent pathways of the gut microbiota-brain axis and neurodegenerative disorders.

Recent research has been uncovering the role of the gut microbiota for brain health and disease. These studies highlight the role of gut microbiota on regulating brain function and behavior through immune, metabolic, and neuronal pathways. In this review we provide an overview of the gut microbiota axis pathways to lay the groundwork for upcoming sessions on the links between the gut microbiota and neurogenerative disorders. We also discuss how the gut microbiota may act as an intermediate factor between the host and the environment to mediate disease onset and neuropathology. Based on the current literature, we further examine the potential for different microbiota-based therapeutic strategies to prevent, to modify, or to halt the progress of neurodegeneration.

Probiotic Properties of Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041 Show Potential to Counteract Functional Gastrointestinal Disorders in an Observational Pilot Trial in Infants.

Functional gastrointestinal disorders (FGIDs) are a common concern during the first year of life. Recognized as gut-brain axis disorders by Rome IV criteria, FGIDs etiology is linked to altered gut-brain interaction, intestinal physiology, and microbiota. In this regard, probiotics have emerged as a promising therapy for infant FGIDs. In this study, we have investigated the probiotic potential of the strains Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041—isolated from healthy children’s feces—in the treatment of FGIDs. To this scope, genome sequences of both strains were obtained and subjected to in silico analyses. No virulence factors were detected for any strain and only the non-transferable erm(49) gene, which confers resistance to erythromycin and clindamycin, was identified in the genome of B. longum KABP042. Safety of both strains was confirmed by acute oral toxicity in rats. In vitro characterization revealed that the strains tolerate gastric and bile challenges and display a great adhesion capacity to human intestinal cells. The two strains mediate adhesion by different mechanisms and, when combined, synergically induce the expression of Caco-2 tight junction proteins. Moreover, growth inhibition experiments demonstrated the ability of the two strains alone and in combination to antagonize diverse Gram-negative and Gram-positive bacterial pathogens during sessile and planktonic growth. Pathogens’ inhibition was mostly mediated by the production of organic acids, but neutralization experiments strongly suggested the presence of additional antimicrobial compounds in probiotic culture supernatants such as the bacteriocin Lantibiotic B, whose gene was detected in the genome of B. longum KABP042. Finally, an exploratory, observational, pilot study involving 36 infants diagnosed with at least one FGID (infant colic and/or functional constipation) showed the probiotic formula was well tolerated and FGID severity was significantly reduced after 14 days of treatment with the 2 strains. Overall, this work provides evidence of the probiotic and synergic properties of strains B. longum KABP042 and P. pentosaceus KABP041, and of their potential to treat pediatric FGIDs.Clinical Trial Registration: [www.ClinicalTrials.gov], [identifier NCT04944628].

Malnutrition-Inflammation Complex Syndrome and Bone Fractures and Cardiovascular Disease Events in Patients Undergoing Hemodialysis: The Q-Cohort Study

Rationale & ObjectiveMalnutrition-inflammation complex syndrome (MICS) is common in patients receiving hemodialysis and increases the risks of morbidity and mortality. However, few studies have examined the overall impact of MICS on disorders of the bone-cardiovascular axis.Study DesignProspective, multicenter, observational cohort study.Setting & ParticipantsA total of 3,030 patients receiving maintenance hemodialysis registered in the Q-Cohort Study.PredictorsA newly developed score for MICS composed of elements chosen from 8 baseline parameters related to nutrition and inflammation by bootstrap resampling, multivariable-adjusted Cox proportional hazard risk analysis for all-cause mortality, and the risk prediction rule. β-coefficients of each element analyzed in the multivariable-adjusted model were used for the creation of the MICS score.OutcomesBone fractures, cardiovascular disease events, and the composite outcome of bone fractures and cardiovascular disease events.Analytical ApproachCox proportional hazard regression and Fine-Gray proportional subdistribution hazards regression.ResultsDuring a median follow-up of 4 years, 140 patients developed bone fractures and 539 developed cardiovascular disease events. Age; serum levels of creatinine, albumin, and C-reactive protein; and body mass index were selected for the creation of the MICS score. The median (IQR) MICS score was 196 (181-212). The multivariable-adjusted Cox proportional hazard risk model and the competing risk model showed that a higher MICS score was incrementally associated with elevated risks of bone fractures, cardiovascular disease events, and the composite outcome; hazard risks (95% CIs) of fractures, cardiovascular disease events, and the composite outcome for each 10-point increase in the MICS score were 1.18 (1.01-1.38), 1.16 (1.07-1.26), and 1.15 (1.07-1.24), respectively.LimitationsOne-time measurement of the parameters used for the creation of the MICS score.ConclusionsMalnutrition and inflammation represented by the MICS score were associated with increased risks of bone-cardiovascular axis disorders in patients receiving maintenance hemodialysis.

A pilot exploration of multi-omics research of gut microbiome in major depressive disorders

The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.

Diarrheal disease and gut microbiome.

Diarrheal disease remains a great public health problem in many countries. Enteric infections caused by several viral, bacterial and parasitic species not only affect the host, but also alter the gut microbiome. The host physiology dictates the intestinal milieu and decides the composition and richness of gut microbiota, which forms a homeostatic ecosystem with numerous functions and provide protection against invading pathogens. During diarrheal infection, patients are affected by gut microbial dysbiosis, which benefits the pathogenic and pro-inflammatory bacteria by enhancing their colonization and proliferation. Gut microbes are associated with several pathophysiological mechanisms, including distorted motility, intestinal barrier dysfunction, malabsorption, immunity disorder, systemic inflammation and changes in the gut-organ axis. Several abiotic factors and childhood malnutrition have negative influences on the gut microbiota, including antibiotics that lead to antibiotic-associated diarrhea and persistent infection. DNA sequencing and bioinformatic analyses enhanced our perception of the gut microbiota, network of metabolic interdependence and their role in health and disease. However, the precise functions of microbiota in gut homeostasis are not well defined. In this chapter, we recapitulate the impact of gut microbiota on diarrheal pathogens, their importance in the immune system and how reshaping the gut microbiota can help during the recovery phase. Additionally, we discuss about impediments and influences beyond diarrhea, particularly on the nutritional status of children.

What do experimental animal models of mood disorders tell clinicians about influence of probiotics on the gut-brain axis?

Abstract It is commonly pointed out that enteric microbiota have a significant impact on the behavioral and neurophysiological parameters relevant to brain-gut axis disorders. Accordingly, many data have demonstrated that probiotics can alter the central nervous system function via this gut-brain axis and commensal bacteria consumption can ameliorate stress-related neuropsychiatric disorders. Thus, modulating the enteric microbiota is increasingly considered a new therapeutic approach for these disorders, although so far there is a lack of reliable pre-clinical and clinical data confirming the usefulness of probiotics in the treatment of affective disorders. In this review, we discuss various mechanisms linking specific probiotic bacteria with behaviors related to anhedonia and the exact mechanisms of their action, including data provided by using animal models and tests. Finally, we point to potential clinical impact resulting from future studies investigating the gut-brain axis activity with respect to the efficacy of probiotic treatment of mental disorders.