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Targeting the Microbiota-Gut-Brain Axis: Emerging Nanomedicine Approaches for Neurodegenerative Diseases.

The microbiota-gut-brain axis (MGBA) is a bidirectional relationship between the gut microbiota (GM) and the brain, where the GM affects the gastrointestinal tract (GIT) and the central nervous system (CNS), and vice versa. Microbiotas are important for several vital body processes, including metabolism, immunity, and homeostasis. The MGBA has three main pathways: the vagal nerve mechanism, the immune-related mechanism, and the neuroendocrine mechanism. GM imbalance, known as dysbiosis, affects the GIT, the brain, and the CNS. Furthermore, dysbiosis is linked to several neurological disorders such as Alzheimer's (AD), Parkinson's (PD), depression, autism spectrum disorder (ASD), and multiple sclerosis (MS). Studying MGBA gives researchers new therapeutic ideas using microbiota. Using special diets rich in fiber and probiotics, in addition to fecal microbiota transplantation (FMT), is being studied as a new therapy for MGBA. From the point of view that these therapeutic interventions maintain microbiota imbalance, which in turn will affect the brain and can relieve the neurological disorders caused by dysbiosis and MGBA.

Humans↗

The effect of probiotic strains on the microbiota of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME).

The aim of the present work was to study five potential probiotic strains (Lactobacillus plantarum, two strains of L. paracasei subsp. paracasei, L. rhamnosus and Bifidobacterium sp.) comparatively in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) in vitro model, and to evaluate this model as a tool in the screening and selection of probiotic bacteria. The impact of the strains on the composition of microbiota and its metabolic activities (production of lactic acid and short-chain fatty acids) was studied. Changes in composition of the microbiota become apparent as a result of probiotic treatment. A marked, but temporary, increase was noted in the number of lactic acid bacteria and bifidobacteria. The profiles of D(-) and L(+) isomers of lactic acid detected in the SHIME after addition of probiotic strains corresponded well to those that are produced in pure culture conditions. The numbers of enterobacteriaceae decreased markedly and those of clostridia detectably during the intervention, while the enterococci tended to increase after the treatment. This pattern was similar in the reactors representing both the small and large intestine in the model. The changes in short-chain fatty acids were small, and no definite trend was observed.

Bifidobacterium↗

Probiotic Lacticaseibacillus casei 2S-1 Attenuates Escherichia coli-Induced Enteritis via Gut Microbiota Modulation and Host Gene Regulation.

Maintaining gut microbial homeostasis is crucial for host health, whereas infection with Escherichia coli (E. coli) is a major contributor to intestinal inflammation and microbial dysbiosis. Recent research has focused on probiotic strategies for managing enteric inflammatory disorders. Previous studies have shown that beneficial microorganisms show protection through modulating host immune responses, enhancing intestinal epithelial barrier integrity, and inhibiting pathogenic bacteria. To evaluate the prophylactic effectiveness of a recently isolated strain, Lacticaseibacillus casei 2S-1, in a murine model of E. coli-induced enteritis, this study focuses on interactions within the microbiota-intestinal-immune axis, together with host transcriptional responses and pathway enrichment associated with oxidative stress and mitochondrial function. In vitro analysis of probiotic features, including growth dynamics, acidogenic capacity, and tolerance to acidic and bile salt environments, as well as genetic safety profiling, followed the methodical isolation and taxonomic identification of L. casei 2S-1. A preventive intervention protocol was established, and a murine model of enteritis was induced by exposure to E. coli. Histopathological analyses were performed to observe in vivo safety and protective efficacy. Changes in gut microbial structure were characterized by 16S rRNA gene sequencing, while host responses were identified by intestinal immunohistochemistry and transcriptome profiling. L. casei 2S-1 showed probiotic properties. In vitro analyses showed that the strain exhibited tolerance to acidic and bile salt conditions, and its untreated culture supernatant showed antimicrobial activity against pathogenic bacteria. Its safety profile was supported by genomic analysis, which verified the lack of virulence-associated genes and antibiotic resistance factors. In vivo, L. casei 2S-1 pretreatment reduced mortality and intestinal inflammation, modulated gut microbial composition, and preserved intestinal barrier-associated protein expression in infected mice. This study provides experimental evidence supporting the prophylactic effects of L. casei 2S-1 and its associations with gut microbiota modulation and host transcriptional responses, providing a foundation for further investigation of probiotic-based preventive strategies against intestinal infections.

Animals↗

Inflammation as the key interface of the medical and nutrition universes: a provocative examination of the future of clinical nutrition and medicine.

There has been tremendous interest in inflammation by researchers, the medical community, and the lay public. Modulation of injury response is felt to represent a tenuous balance of pro- and anti-inflammatory cytokines. Adverse outcomes may result from severe, sustained, or repeated bouts of inflammation. A critical observation is that nutrition support alone is inadequate to prevent muscle loss during active inflammation. It is necessary to take inflammation into consideration in conducting appropriate nutrition assessment, intervention, and monitoring. A host of medical conditions are actually inflammatory states that have important implications for nutrition care. Multifaceted interventions that may include anti-inflammatory diets, glycemic control, physical activity, appetite stimulants, anabolic agents, anti-inflammatory agents, anticytokines, and probiotics, will be necessary to blunt undesirable aspects of inflammatory response to preserve body cell mass and vital organ functions. Nutrition practitioners can seize this opportunity to be a part of the future medical team that brings highly individualized patient care to the bedside.

Forecasting↗

Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics.

OBJECTIVE: In Irritable Bowel Syndrome, the gut-associated immune system may be up-regulated resulting in immune complex production, low-grade inflammation, loss of Class I bacteria, and translocation of inflammatory mediators and macromolecules outside of the GI lumen. Since food intolerance may be one of the reasons for this upregulation, our goal was to investigate the role of food intolerance in IBS patients. METHODS: In this open label pilot study, we enrolled 20 patients with IBS by Rome II criteria (15 women, ages 24-81) who had failed standard medical therapies in a tertiary care GI clinic. Baseline serum IgE and IgG food and mold panels, and comprehensive stool analysis (CSA) were performed. Breath-hydrogen testing and IBS Quality-of-Life (QOL) questionnaires were obtained. Patients underwent food elimination diets based on the results of food and mold panels followed by controlled food challenge. Probiotics were also introduced. Repeat testing was performed at 6-months. We followed up with this cohort at 1 year after trial completion to assess the reported intervention and for placebo effect. RESULTS: Baseline abnormalities were identified on serum IgG food and mold panels in 100% of the study subjects with significant improvement after food elimination and rotation diet (p < 0.05). Significant improvements were seen in stool frequency (p < 0.05), pain (p < 0.05), and IBS-QOL scores (p < 0.0001). Imbalances of beneficial flora and dysbiotic flora were identified in 100% of subjects by CSA. There was a trend to improvement of beneficial flora after treatment but no change in dysbiotic flora. The 1-year follow up demonstrated significant continued adherence to the food rotation diet (4.00 +/- 1.45), minimal symptomatic problems with IBS (4.00 +/- 1.17), and perception of control over IBS (4.15 +/- 1.23). The continued use of probiotics was considered less helpful (3.40 +/- 1.60). CONCLUSION: These data demonstrate that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical response and impacts on overall well being and quality of life in this challenging entity.

Adult↗

Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children.

Lactobacillus rhamnosus GG, ATCC (LGG), has shown antagonism to many bacteria including mutans streptococci. This randomized, double-blind, placebo-controlled intervention study was designed to examine whether milk containing LGG has an effect on caries and the risk of caries in children when compared with normal milk. 594 children, 1-6 years old, from 18 municipal day-care centres were included. The children received the milk with meals from coded containers 5 days a week in the day-care centres for 7 months. The children's oral health was recorded at baseline and at the end, using WHO criteria. The caries risk was calculated based on clinical and microbiological data, comprising mutans streptococcus levels from dental plaque and saliva. The risk was classified as high if the child had a dmft/DMFT or initial caries score >0, and a mutans streptococcus count > or = 10(5) CFU/ml. The results showed less dental caries in the LGG group and lower mutans streptococcus counts at the end of the study. LGG was found to reduce the risk of caries significantly (OR = 0.56, p = 0.01; controlled for age and gender, OR = 0.51, p = 0.004). The effect was particularly clear in the 3- to 4-year-olds. Thus, milk containing the probiotic LGG bacteria may have beneficial effects on children's dental health.

Age Factors↗

Pharmacogenomic strategies against resistance development in microbial infections.

There are several promising new strategies against resistance development in microbial infections. This paper discusses typical experimental and bioinformatical strategies to study the impact of infectious challenges on host-pathogen interaction, followed by several novel approaches and sources for new pharmaceutical strategies against resistance development. Genomics reveals promising new targets by providing a better understanding of cellular pathways, through the identification of new pathways, and by identifying new intervention areas, such as phospholipids, glycolipids, innate immunity, and antibiotic peptides. Additional antibiotic resources come from new genomes, including marine organisms, lytic phages and probiotic strategies. A system perspective regards all interactions between the host, pathogen and environment to develop new pharmacogenomic strategies against resistance development.

Animals↗

Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG.

Lactobacillus bacteremia is a rare entity, and its clinical significance is poorly defined. We have reviewed the risk factors and outcome for 89 case patients with Lactobacillus bacteremia. Species characterization was done in 53% of the cases, revealing 25 L. rhamnosus strains and 22 other Lactobacillus species. In 11 cases, the strain was identical with the probiotic L. rhamnosus GG. In 82% of the cases, the patients had severe or fatal comorbidities. Predisposing factors to bacteremia were immunosuppression, prior prolonged hospitalization, and prior surgical interventions. No significant differences were observed in these predisposing factors or clinical features between patients with cases associated with the various Lactobacillus species, other than higher C-reactive protein values in patients with L. rhamnosus bacteremia. Mortality was 26% at 1 month and was 48% at 1 year. In multivariate analysis, severe underlying diseases were a significant predictor for mortality (odds ratio [OR], 15.8), whereas treatment with antimicrobials effective in vitro was associated with lower mortality (OR, 0.22). We conclude that lactobacilli in blood cultures are of clinical significance and that their susceptibility should guide decisions about antimicrobial treatment.

Anti-Bacterial Agents↗

Primary dietary prevention of food allergy.

OBJECTIVE: To present research and clinical evidence on the use of primary dietary prevention in food allergy management. DATA SOURCES: We conducted MEDLINE searches for pertinent articles published between January 1986 and October 2001 with use of the following keywords or phrases: prevention and diet and allergy, food allergy and prevention, and dietary prevention and food allergy or allergens. Also included are information and commentary reflecting the authors' cumulative clinical experience in an allergy unit of a city hospital. RESULTS: We define as "proactive" those strategies centered on "success factors," such as the early postnatal environment, prolonged breast-feeding, and use of formula and probiotic supplementation, in contrast to earlier "prohibitionist" approaches to prevention of food allergy. These two approaches are not antagonistic and may even be synergistic. We introduce this distinction in light of epidemiologic evidence and out of concern about compliance and the quality of life for patients. CONCLUSIONS: Inasmuch as nutritional and immune maturation are implicated, the prohibitionist measures that are most effective in primary prevention of food allergy are exclusive breast-feeding for at least 6 months (for lifelong immunity and other benefits), delayed (after the sixth month) introduction of solid foods, and on-indication use of "hypoallergenic" formulas. Whether proactive strategies can be contemplated remains a debatable issue. Evidence for and against the scientific use of probiotics as well as microbiologic, epidemiologic, and clinical data are discussed. Review of published epidemiologic studies and randomized clinical trials is essential before planning dietary intervention or prevention.

Allergens↗

Microecology as a target for therapeutic intervention in inflammatory bowel disease.

The gastrointestinal tract is populated by several hundred grams of bacteria. Recognition of the symbiosis between bacteria and host is drawing particular attention to the implications of bacteria in human health. Probiotics are living microorganisms that upon ingestion in certain numbers exert health benefits. Prebiotics are non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth or activity of a limited number of gut bacteria. In inflammatory bowel disease (IBD), the gut flora is the key factor driving the inflammatory process that leads to intestinal lesions. Interaction of certain commensal bacteria with the gut mucosa triggers mucosal inflammation. However, certain probiotic strains are able to downregulate inflammatory pathways. Restoring the microbial balance with prebiotics and probiotics offers promise for the control of IBD.

Animals↗

Immune responses and vaccination against periodontal infections.

BACKGROUND: The infectious aetiology of periodontitis is complex and no curative treatment modality exists. Palliative therapy is available. AIMS: To review the evidence that active or passive immunization against periodontitis provides immune protection. MATERIAL AND METHODS: PubMed (Medline), the National Institutes of Health, the Food and Drug Administration, and the Center for Disease Control electronic databases were searched to extrapolate information on immune responses to immunization against periodontitis. RESULTS: Studies in non-human primate models using ligature-induced experimental periodontitis suggest that antibody responses by active immunization against Porphyromonas gingivalis can safely be induced, enhanced, and obtained over time. Immune responses to whole bacterial cell and purified protein preparations considered as vaccine candidates have been evaluated in different animal models demonstrating that there are several valid vaccine candidates. Data suggest that immunization reduces the rate and severity of bone loss. It is also, temporarily, possible to alter the composition of the subgingival microflora. Natural active immunization by therapeutic interventions results in antibody titre enhancement and potentially improves treatment outcomes. Passive immunization of humans using P. gingivalis monoclonal antibodies temporarily prevents colonization of P. gingivalis. Probiotic therapy may be an alternative approach. Regulatory and safety issues for human periodontal vaccine trials must be considered. Shared infectious aetiology between periodontitis and systemic diseases may enhance vaccine effort developments. CONCLUSIONS: Proof of principle that active and passive immunization can induce protective antibody responses is given. The impact of natural immunization and passive immunization in humans should be explored and may, presently, be more feasible than active immunization studies.

Animals↗

[The veterinarian active in the field of veterinary public health, towards the year 2000].

Introductory classes taught to seventeen successive generations of postgraduate veterinary students, intensive consultations, during about 40 years, with scientists in executive positions in the food industry, catering and military-medical organisations, and the response of participants after public lectures support the impression that, in the Netherlands, the public is not aware of the professional profile of the Public Health Veterinarian. This contrasts sharply to that of the small animal practitioner and of the herd management veterinarian. In the years immediately before the Second World War the professional standing of the Veterinary Public Health Officer was demonstrably better observable. The reason for this altered public image of the Public Health Veterinarian is sought in changes in the aetiology and transmission of zoonoses and other diseases spread by food, water and the environment. Whereas the majority of the latter was previously transmitted off intra vitam foci of infection, food-borne infections and intoxications presently mainly originate from the environment. Consequently adequate protection of the consumer has to rely on the elaboration and application of measures of intervention sensu Wilson. These include: well designed techniques of hygiene supported by disinfection at the farm and during transportation and holding animals for slaughter, use of probiotics in decontaminated animal feeds, meticulous adherence to expertly designed measures of hygiene and chilling at slaughter houses and, to the extent required, terminal decontamination of carcasses and/or consumer size cuts. Many of these facets do not traditionally belong to the veterinarian's vistas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dietary cancer and prevention using antimutagens.

Many of the cancers common in the Western world, including colon, prostate and breast cancers, are thought to relate to dietary habits. Of the known risk factors, many will act through increasing the probability of mutation. Recognised dietary mutagens include cooked meat compounds, N-nitroso compounds and fungal toxins, while high meat and saturated fat consumption, increasing rates of obesity, and regular consumption of alcohol and tobacco are all dietary trends that could indirectly enhance the probability of mutation. However, there are significant difficulties in implementing and sustaining major dietary changes necessary to reduce the population's intake of dietary mutagens. Dietary antimutagens may provide a means of slowing progression toward cancer, and be more acceptable to the population. Consideration of genetic mechanisms in cancer development suggest several distinct targets for intervention. Strategies that reduce mutagen uptake may be the most simple intervention, and the one least likely to result in undesirable side effects. Certain (but not all) types of dietary fibres appear to reduce mutation through this mechanism, as may certain probiotics and large planar molecules such as chlorophyllin. Antioxidants have been suggested to scavenge free radicals, and prevent their interactions with cellular DNA. Small molecule dietary antioxidants include ascorbic acid, Vitamin E, glutathione, various polyphenols and carotenoids. We found a statistically significant relationship between colon cancer incidence and soil selenium status across different regions of New Zealand. Additionally, a study of middle-aged men suggested that blood selenium levels lower than 100 ng/ml were inadequate for repair or surveillance of oxidative (and other) DNA damage. We suggest that selenium will be an important antimutagen, at least in New Zealand, possibly through antioxidant effects associated with selenium's role in enzymes associated with endogenous repair of DNA damage. Modulation of xenobiotic metabolizing enzymes is well recognised as cancer-protective, and is a property of various flavonoids and a number of sulfur-containing compounds. Many fruits and vegetables contain compounds that will protect against mutation and cancer by several mechanisms. For example, kiwifruit has antioxidant effects and may also affect DNA repair enzymes. Dietary folate may be a key factor in maintenance of methylation status, while enhanced overall levels of vitamins and minerals may retard the development of genomic instability. The combination of each of these factors could provide a sustainable intervention that might usefully delay the development of cancer in New Zealand and other populations. Although there are a range of potentially antimutagenic fruits, vegetables and cereals available to these populations, current intake is generally below the level necessary to protect from dietary or endogenous mutagens. Dietary supplementation may provide an alternative approach.

Adolescent↗

Role of intestinal flora in the development of allergy.

PURPOSE OF REVIEW: The frequency of allergic diseases is increasing worldwide. Experimental and clinical studies have linked a reduced number of early infections to this trend. The gastrointestinal system, which comprises the largest lymphoid tissue and microbial reservoir of the body, has received more attention during the last few years as a potential determiner in the development of atopic disease. RECENT FINDINGS: Alterations in intestinal microbiota have been detected both in infants suffering from allergic disease and in those later developing the disorder. Delay in the compositional development of and in gut microflora was a general finding in allergic children. In a subsequent study, perinatal administration of lactobacilli halved the later development of atopic eczema during the first 2 years of life. Specific strains of the healthy gut microbiota have been shown to induce the production of IL-10 and transforming growth factor-beta, which possess an important regulative role in the development of allergic type immune response. Probiotics also strengthen gut defence barrier mechanisms and reduce antigen load in the gut. Pattern recognition receptors in intestinal epithelial and antigen-presenting cells have been demonstrated to mediate a continuing dialogue between host and gut microbiota. SUMMARY: Despite several promising findings, the exact role of gut normal microbiota in the development of allergy remains to be elucidated. For successful interventions, more data concerning a communication between host and specific microbial species are needed.

Animals↗

Decoding the spatiotemporal patterns of food spoilage microbial communities: Integrating multi-omics and artificial intelligence to enable precision preservation.

In the global food supply chain, food wastage caused by spoilage has resulted in significant economic losses, food shortages, and environmental pressure. This process is fundamentally driven by the spatiotemporal dynamics of microbial communities. However, traditional research methods struggle to elucidate the complex mechanisms of spatial heterogeneity, interspecies interactions, and functional succession. This limits the development of effective preservation strategies. This review systematically reviews the cutting-edge progress of integrating multi-omics technologies and artificial intelligence (AI) to study food spoilage microbial communities, breaking through this bottleneck. We propose an intelligent theoretical framework that could potentially analyze microbial metabolic activities and predict dynamic shelf life if implemented. The conceptual framework integrates multidimensional data, including spatial metabolomics, temporal metatranscriptomics, single-cell transcriptomics, and longitudinal metagenomics. It can also be combined with AI models, such as graph neural networks. The article elaborates on the principles and applications of spatio-temporal monitoring technologies, such as nano secondary ion mass spectrometry, hyperspectral imaging, and the Internet of Things sensing. Through illustrative cases of typical perishable foods, it also explores how such a multi-omics - AI system might be applied to spoilage warning and precise intervention. Additionally, the article addresses the current challenges in data coverage, model generalization, and federated learning implementation. Then the research further explores emerging areas such as engineered probiotics, edge AI, and microfluidic sensing. These areas are targeted at transforming food preservation from an empirical control approach to a data-driven, precise regulatory framework. This transformation provides theoretical support and technical approaches for developing a smart, sustainable food preservation system.

Multiomics↗

Nutrition support for pediatric patients with inflammatory bowel disease: a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology And Nutrition.

Impairment of growth and malnutrition are significant complications of inflammatory bowel disease (IBD) in pediatric patients. Since this topic was last reviewed in these pages (), a number of studies have further explored the epidemiology and pathogenesis of these nutritional complications of IBD in an effort to provide more effective interventions to prevent the long-term consequences of chronic nutrient deficiencies in childhood. In addition, during the past 15 years, the use of selected nutrients and microorganisms (probiotics) as primary or adjunctive therapy for the treatment of IBD has become an emerging area of great interest. The following is a Clinical Report from the Nutrition and Inflammatory Bowel Disease Committees of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Body Height↗

Guidelines for adults on self-medication for the treatment of acute diarrhoea.

Acute uncomplicated diarrhoea is commonly treated by self-medication. Guidelines for treatment exist, but are inconsistent, sometimes contradictory, and often owe more to dogma than evidence. An ad hoc multidisciplinary group has reviewed the literature to determine best practice. In general it is recognized that treatment of acute episodes relieves discomfort and social dysfunction. There is no evidence that it prolongs the illness. Self-medication in otherwise healthy adults is safe. Oral loperamide is the treatment of choice. Older anti-diarrhoeal drugs are also effective in the relief of symptoms but carry the risk of unwanted adverse effects. Oral rehydration solutions do not relieve diarrhoea, and confer no added benefit for adults who can maintain their fluid intake. Probiotic agents are, at present, limited in efficacy and availability. Antimicrobial drugs, available without prescription in some countries, are not generally appropriate for self-medication, except for travellers on the basis of medical advice prior to departure. Medical intervention is recommended for the management of acute diarrhoea in the frail, the elderly (> 75 years), persons with concurrent chronic disease, and children. Medical intervention is also required when there is no abatement of the symptoms after 48 h, or when there is evidence of deterioration such as dehydration, abdominal distension, or the onset of dysentery (pyrexia > 38.5 degrees C and/or bloody stools).

Acute Disease↗

Current controversies in the understanding of necrotizing enterocolitis. Part 1.

Necrotizing enterocolitis (NEC) has widespread implications for neonates. While mostly affecting preterm neonates, full-term neonates, especially those with congenital heart disease, are also at risk. Although the exact pathogenesis of NEC remains elusive, three major factors, a pathogenic organism, enteral feedings, and bowel compromise, coalesce in at-risk neonates to produce bowel injury. Initiation of the inflammatory cascade likely serves as a common pathway for the disorder. Clinical signs and symptoms range from mild feeding intolerance with abdominal distension to catastrophic disease with bowel perforation, peritonitis, and cardiovascular collapse. Vigilant assessment of at-risk neonates is crucial. When conservative medical management fails to halt injury, surgical intervention is often needed. Strategies to decrease the incidence and ultimately prevent NEC loom on the horizon, such as exclusive use of human breastmilk for enteral feedings and administration of probiotics.

Australia↗