Influence of the gut microbiota on satiety signaling

Recent studies show a link between the gut microbiota and the regulation of satiety and energy intake, processes that contribute to the development and pathophysiology of metabolic diseases. However, this link is predominantly established in animal and in vitro studies, whereas human intervention studies are scarce. In this review we focus on recent evidence linking satiety and the gut microbiome, with specific emphasis on gut microbial short-chain fatty acids (SCFAs). Based on a systematic search we provide an overview of human studies linking the intake of prebiotics with gut microbial alterations and satiety signaling. Our outcomes highlight the importance of in-depth examination of the gut microbiota in relation to satiety and provide insights into recent and future studies in this field.     

The intestinal microbiota and chronic disorders of the gut

Mucosal surfaces of the gut are colonized by large numbers of heterogeneous bacteria that contribute to intestinal health and disease. In genetically susceptible individuals, a 'pathogenic community' may arise, whereby abnormal gut flora contributes to alterations in the mucosa and local immune system leading to gastrointestinal disease. These diseases include enteric infections, such as Clostridium difficile infection, small intestinal bacterial overgrowth, functional gastrointestinal disorders (including IBS), IBD and colorectal cancer. Prebiotics, probiotics and synbiotics (a combination of prebiotics and probiotics) have the capacity to reverse pathologic changes in gut flora and local immunity. Intestinal health and disease need to be thoroughly characterized to understand the interplay between the indigenous microbiota, the immune system and genetic host factors. This Review provides a broad overview of the importance of the intestinal microbiota in chronic disorders of the gut.     

Influence of mother's intestinal microbiota on gut colonization in the infant

The aim here was to elucidate the mother-infant association in the gut colonization of 1-6 month-old infants and to establish whether probiotics can influence this process. Fecal samples from 80 mother-infant pairs were analyzed at 1 month (mothers and infants) and 6 months (infants) by real-time polymerase chain reaction to assess bacterial numbers. This double-blind placebo-controlled trial involved 2 different probiotic combinations (1. Lactobacillus rhamnosus + Bifidobacterium longum and 2. Lactobacillus paracasei + Bifidobacterium longum) given to the mothers 2 months prior to and 2 months after delivery. Bifidobacterium bifidum colonization in the mothers significantly increased the infants' probability of being colonized by B. bifidum and their bifidobacterial diversity indexes (DI) and the mother-infant similarity indexes (SI) both at 1 and 6 months of age. The counts of Bifidobacterium genus (at 1 month) and Bifidobacterium longum (at 6 months) correlated between mothers and infants. At 6 months, a significant effect of the probiotic intervention was found in the mother-infant association of fecal bifidobacterial counts but not in the colonization frequencies, DI or SI. In conclusion, a clear association between mother and infant was found in gut colonization by bifidobacteria. Maternal colonization by B. bifidum had the most consistent effects on the infant's bifidobacterial microbiota. Maternal probiotic treatment had little effect on this mother-infant association.     

Influence of mother's intestinal microbiota on gut colonization in the infant

The aim here was to elucidate the mother-infant association in the gut colonization of 1-6 month-old infants and to establish whether probiotics can influence this process. Fecal samples from 80 mother-infant pairs were analyzed at 1 month (mothers and infants) and 6 months (infants) by real-time polymerase chain reaction to assess bacterial numbers. This double-blind placebo-controlled trial involved 2 different probiotic combinations (1. Lactobacillus rhamnosus + Bifidobacterium longum and 2. Lactobacillus paracasei + Bifidobacterium longum) given to the mothers 2 months prior to and 2 months after delivery. Bifidobacterium bifidum colonization in the mothers significantly increased the infants' probability of being colonized by B. bifidum and their bifidobacterial diversity indexes (DI) and the mother-infant similarity indexes (SI) both at 1 and 6 months of age. The counts of Bifidobacterium genus (at 1 month) and Bifidobacterium longum (at 6 months) correlated between mothers and infants. At 6 months, a significant effect of the probiotic intervention was found in the mother-infant association of fecal bifidobacterial counts but not in the colonization frequencies, DI or SI. In conclusion, a clear association between mother and infant was found in gut colonization by bifidobacteria. Maternal colonization by B. bifidum had the most consistent effects on the infant's bifidobacterial microbiota. Maternal probiotic treatment had little effect on this mother-infant association.     

Functional analysis of gut microbiota and immunoinflammation in children with autism spectrum disorders

Background and AimsRecent evidence implicates gut microbiota (GM) and immune alterations in autism spectrum disorders (ASD). We assess GM profile and peripheral levels of immunological, neuronal and bacterial molecules in ASD children and controls. Alarmin HMGB1 was explored as a non-invasive biomarker to monitor gastrointestinal (GI) symptoms.MethodsThirty ASD children and 14 controls entered into the study. GM metagenomic analysis was performed for 16 ASD patients and 7 controls. GM functional profile was assessed by GO term analysis. Blood levels of IL-1β, TNFα, TGFβ, IL-10, INFγ, IL-8, lipopolysaccharide, Neurotensin, Sortilin1 and GSSG/GSH ratio were analyzed in all subjects by ELISA. Fecal HMGB1 was analyzed by Western blot.ResultsWe observed a significant decrease in bacterial diversity. Furthermore, 82 GO terms underrepresented in ASD. Four of them pointed at 3,3 phenylpropionate catabolism and were imputable to Escherichia coli (E. coli) group. Serum levels of TNFα, TGFβ, NT, and SORT-1 increased in ASD patients. Fecal levels of HMGB1 correlated with GI sign severity in ASD children.ConclusionsWe suggest that a decrease of E. coli might affect the propionate catabolism in ASD. We report occurrence of peripheral inflammation in ASD children. We propose fecal HMGB1 as a non-invasive biomarker to detect GI symptoms.     

Air pollution effects on the gut microbiota

Global incidence rates for inflammatory bowel disease (IBD) have gradually risen over the past 20 years. Genome-wide association studies (GWAS) have identified over 160 genetic loci associated with IBD; however, inherited factors only account for a partial contribution to the disease risk. We have recently shown that urban airborne particulate matter (PM) ingested via contaminated food can alter gut microbiome and immune function under normal and inflammatory conditions. In this addendum, we will discuss how PM can modify the gut microbial form and function, provide evidence on changes seen in intestinal barrier, and suggest a working hypothesis of how pollutants affect the gastrointestinal tract. The significance of the work presented could lead to identifying airborne pollutants as potential risk factors and thus provide better patient care management.     

Uveitis and the gut microbiota

Uveitis is a heterogeneous collection of inflammatory diseases of the intraocular uveal tissues and adjacent structures, and they collectively are a significant cause of visual morbidity. In recent years, investigating the contribution of the gut microbiota to autoimmunity, including the development of uveitis, has gained interest. Decreased disease severity has been observed in both the induced experimental autoimmune model of uveitis and the spontaneous RI61H model of uveitis in mice treated with oral broad-spectrum antibiotics and raised in germ-free conditions, implicating a role for the gut microbiota in the development of disease in these models. Also, in support of these findings are the differences in the composition of the microbiota that have been reported in uveitis patients. Proposed mechanisms accounting for the microbiota triggering uveitis include antigenic mimicry and dysbiosis leading to dysregulation of the immune system. An improved understanding of these mechanisms will facilitate potential therapeutic approaches including alteration of the microbiota with probiotic treatment and fecal microbiota transplants.     

HIV-induced alteration in gut microbiota

Consistent with an important role for adaptive immunity in modulating interactions between intestinal bacteria and host, dramatic alteration in the composition of gut microbes during chronic HIV infection was recently reported by ourselves and independently by four other research groups. Here we evaluate our results in the context of these other studies and delve into the effects of antiretroviral therapy (ART). Although gut microbiota of HIV-positive individuals on ART usually does not resemble that of HIV-negative individuals, the degree to which ART restores health-associated prevalence varies across bacterial taxa. Finally, we discuss potential drivers and health consequences of gut microbiota alterations. We propose that understanding the mechanism of HIV-associated gut microbiota changes will elucidate the role of adaptive immunity in shaping gut microbiota composition, and lay the foundation for therapeutics targeting the microbiota to attenuate HIV disease progression and reduce the risk of gut-linked disease in people with HIV.     

Impact of Helicobacter pylori infection on gut microbiota

A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.     

role of the normal gut microbiota

Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include(1) the mode of delivery(vaginal or caesarean);(2) diet during infancy(breast milk or formula feeds) and adulthood(vegan based or meat based); and(3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.     

Chemical conversations in the gut microbiota

The gut microbiota is a complex, densely populated community, home to many different species that collectively provide huge benefits for host health. Disruptions to this community, as can result from recurrent antibiotic exposure, alter the existing network of interactions between bacteria and can render this community susceptible to invading pathogens. Recent findings show that direct antagonistic and metabolic interactions play a critical role in shaping the microbiota. However, the part played by quorum sensing, a means of regulating bacterial behavior through secreted chemical signals, remains largely unknown. We have recently shown that the interspecies signal, autoinducer-2 (AI-2), can modulate the structure of the gut microbiota by using Escherichia coli to manipulate signal levels. Here, we discuss how AI-2 could influence bacterial behaviors to restore the balance between the 2 major bacteria phyla, the Bacteroidetes and Firmicutes, following antibiotic treatment. We explore how this may impact on host physiology, community susceptibility or resistance to pathogens, and the broader potential of AI-2 as a means to redress the imbalances in microbiota composition that feature in many infectious and non-infectious diseases.     

Diabetes,obesity and gut microbiota

The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes.     

Corticosteroid-induced neuropsychiatric disorders: review and contrast with neuropsychiatric lupus

The aim of this review is to analyze the available literature regarding the neuropsychiatric (NP) disturbances associated with corticosteroid (CS) therapy; to determine the nature, severity, and frequency of these NP symptoms; and to identify the various risk factors involved in the development of CS-induced NP disturbances. We searched the available literature since the advent of corticosteroid therapy (1950) utilizing the PubMed database (www.pubmed.gov). Primary articles were identified, and they and their pertinent references were reviewed. Due to potential confusion between NP manifestations of CS therapy and central nervous system (CNS) involvement of systemic lupus erythematosus (SLE), a condition often treated with CS, a brief review of NP manifestations of SLE was also performed. The presentation of CS-induced neuropsychiatric disorders (CIPD) can be quite varied with depression, hypomania, and overt psychosis being the most common manifestations. CIPD can also include bipolar affective changes, delirium, panic attacks, agoraphobia, obsessive–compulsive disorder, anxiety, insomnia, restlessness, fatigue, catatonia, reversible dementia-like cognitive changes, impaired memory, and concentration. No factors have been identified that allow for the accurate prediction of development of CIPD. A dose-dependent relationship (increased risk when the daily prednisone-equivalent dose is ≥40 mg) has been observed in most cases of CIPD, although there have been case reports with lower doses, alternate-day therapy, and even inhaled CS. Women are more commonly affected with most symptoms occurring in the first 6 weeks of starting treatment. SLE has been the only specific illness that has been linked to a greater risk of CIPD and the NP manifestations of SLE may mimic those of CIPD, with most occurring in the first year of diagnosis. Antiribosomal P, antineuronal, or antiphospholipid antibodies are frequently seen in patients with SLE developing CIPD. Imaging and EEG abnormalities, the coexistence of non-CNS manifestations of SLE, and the presence of serious disturbances in memory and concentration are more suggestive of NP–SLE than CIPD. Although NP symptoms associated with the use of CS generally resolve with discontinuation of the medication, prophylaxis with lithium, and treatment with antidepressants, anticonvulsants and electroconvulsive therapy for severe mania and depression have been reported with successful outcomes. A greater understanding of the underlying mechanism of CIPD, risk factors involved, treatment options, and the distinguishing features from NP–SLE will ultimately lead to more directed therapy for such patients.     

肠道菌群与脓毒症相互关系的研究进展

脓毒症的发生发展与肠道菌群失调密切相关.肠道菌群失调可以通过肠黏膜屏障功能破坏、黏膜免疫功能破坏和细菌移位等环节诱导脓毒症的发生.同时脓毒症也可以加重肠道菌群失调,加重肠黏膜屏障功能破坏,导致机体多器官功能障碍.本文通过探讨肠道菌群和脓毒症之间的相互关系,为脓毒症临床干预提供思路.