Periodontitis is widely acknowledged as the most prevalent type of oral inflammation, arising from the dynamic interplay between oral pathogens and the host's immune responses. It is also recognized as a contributing factor to various systemic diseases. Dysbiosis of the oral microbiota can significantly alter the composition and diversity of the gut microbiota. Researchers have delved into the links between periodontitis and systemic diseases through the "oral-gut" axis. However, whether the associations between periodontitis and the gut microbiota are simply correlative or driven by causative mechanistic interactions remains uncertain. This review investigates how dysbiosis of the gut microbiota impacts periodontitis, drawing on existing preclinical and clinical data. This study highlights potential mechanisms of this interaction, including alterations in subgingival microbiota, oral mucosal barrier function, neutrophil activity, and abnormal T-cell recycling, and offers new perspectives for managing periodontitis, especially in cases linked to systemic diseases.

Yes-associated protein 1 (YAP1) regulates the survival, proliferation, and stemness of cells, and contributes to the development of metabolic dysfunction associated fatty liver disease (MAFLD). However, the regulatory role of intestinal YAP1 in MAFLD still remains unclear.

Terminal ileal specimens were used to compare intestinal YAP1 activation in patients with and without MAFLD. Mice targeted for knocking out YAP1 in the intestinal epithelium were fed a high-fat diet (HFD) for 8 consecutive weeks. In a separate group, the mice were fed an HFD supplemented with the bile acid binder cholestyramine (CHO) or a low-fat diet with deoxycholic acid (DCA). Immunofluorescence, Immunohistochemistry, Western blot, RT-qPCR, ELISA, 16S rDNA sequencing, tissue and enteroid culture techniques were used to evaluate the effects of an HFD or DCA on the gut‒liver axis in mice or humans.

Intestinal YAP1 was activated in both humans with MAFLD and mice fed an HFD. In in vivo studies, YAP1 knockout in intestinal epithelial cells of mice alleviated the hepatic steatosis induced by an HFD, and mitigated the adverse effects of HFD on the gut‒liver axis, including the upregulation of lipopolysaccharide (LPS) and inflammation levels, enrichment of intestinal Gram-negative bacteria, and inhibition of intestinal stem cell (ISC) differentiation into the goblet and Paneth cells. High-fat feeding (HFF) produced high concentrations of DCA. The consumption of DCA mimics these HFF-induced changes, and is accompanied by the activation of Abelson tyrosine-protein kinase 1 (ABL1) and its direct substrate, YAP1, in the terminal ileum. In vitro studies further confirmed that DCA upregulated the tyrosine phosphorylation of YAP1Y357 in ISC by activating ABL1, which inhibited the differentiation of ISCs into secretory cells.

Our findings reveal that the activation of the ABL1‒YAP1 axis in ISCs by DCA contributes to hepatic steatosis through the gut‒liver axis, which may provide a potential intestinal therapeutic target for MAFLD.

An increasingly important role for gut microbiota in the initiation and progression of colorectal cancer (CRC) has been described. Even in the early stages of transformation, i.e., colorectal adenomas, changes in gut microbiota composition have been observed, and several bacterial species, such as pks+Escherichia coli and enterotoxigenic Bacteroides fragilis, have been proposed to drive colon tumorigenesis. In recent years, several strategies have been developed to study mucosa-associated microbiota (MAM), which is more closely associated with CRC development than lumen-associated microbiota (LAM) derived from fecal samples. This review summarizes the state of the art about the oncogenic actions of gut bacteria and compares the different sampling strategies to collect intestinal microbiota (feces, biopsies, swabs, brushes, and washing aspirates). In particular, this article recapitulates the current knowledge on MAM in colorectal adenomas and serrated polyps, since studying the intestinal microbiota associated with early-stage tumors can elucidate the molecular mechanisms underpinning CRC carcinogenesis.

Aronia Melanocarpa (Michx.) Elliott fruit has been extensively used in the food and medicinal fields. This study aimed to analyze the physicochemical properties of a polysaccharide fraction (AMP2) isolated from this fruit for the first time and investigated its immune regulatory mechanism. The physicochemical properties of AMP2 were determined using high-performance gel permeation chromatography, PMP derivatization-high performance liquid chromatography, Ultraviolet spectroscopy, and infrared spectroscopy. The metagenomic technology was applied to investigate the regulatory effects and mechanisms of AMP2 on the gut microbiota of immunosuppressed mice. The results showed that molecular weight of AMP2 was 83,444 Da, which was mainly composed of D-arabinose, D-xylose, D-mannose, D-rhamnose and D-glucose, and both β-type and α-type glycosidic bonds contained in its structure. AMP2 changed the composition of gut microbiota by increasing the number of beneficial and probiotic bacteria, thereby regulated the intestinal mucosal immune system of host. AMP2 improved intestinal immune system response and antimicrobial capacity through positive regulation of the NOD-like receptor signaling pathway and neutrophil extracellular trap formation. The results demonstrate the potential of AMP2 in immune regulation, providing a new perspective for its subsequent development and contributing to the development and application of related health foods.

The prevalence and severity of periodontitis are increased and advanced in diabetes. Severe periodontitis elicits adverse effects on diabetes by impairing insulin actions due to systemic microinflammation. Recent studies unveil the emerging findings and molecular basis of the bidirectional relationship between periodontitis and diabetes. In addition to conventional mechanisms such as hyperglycemia, hyperlipidemia, and chronic inflammation, deficient insulin action may play a pathogenic role in the progression of periodontitis under diabetes. Epidemiologically, from the viewpoint of the adverse effect of periodontitis on diabetes, recent studies have suggested that Asians including Japanese and Asian Americans with diabetes and mild obesity (BMI <25 kg/m2) should pay more attention to their increased risk for cardiovascular diseases. In this review, we summarize recent findings on the effect of diabetes on periodontitis from the viewpoint of abnormalities in metabolism and insulin resistance with novel mechanisms, and the influence of periodontitis on diabetes mainly focused on micro-inflammation related to mature adipose tissue and discuss future perspectives about novel approaches to interrupt the adverse interrelationship.

High-fat diet (HFD)-induced obesity is a global health concern associated with gastrointestinal disorders. While mammalian models have elucidated the effects of a HFD on intestinal structure and function, its impact on zebrafish, a crucial model for studying diet-induced obesity and gastrointestinal dysfunction, remains inadequately characterized. This study investigated the influence of a HFD on zebrafish intestinal morphology, tight junction (TJ) protein expression, and inflammatory markers. Zebrafish fed a control diet or HFD with 40% or 60% fat exhibited significant alterations in intestinal morphology, with increased villi number but reduced villi width and length, suggesting compensatory responses to dietary stress. TJ protein expression (Claudin 2, Claudin 3, and Claudin 10) showed complex changes, particularly in the HFD60 juvenile group, indicating a multifaceted response in barrier integrity. Pro-inflammatory cytokine IL-6 and TNF-α levels were lower in both the juvenile and adult HFD60 groups than in the HFD40 and control groups, while elevated anti-inflammatory IL-10 levels in HFD60 adult zebrafish suggested activation of compensatory mechanisms. These findings highlight zebrafish as a valuable model for studying the effects of HFD on intestinal health and provide insights into the relationship between dietary fat, gut dysfunction, and inflammation.

The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host at both the gut and systemic levels. The gut microbiome, which is primarily made up of commensal bacteria, is critical for maintaining the healthy host's immune system, aiding digestion, synthesizing essential nutrients, and protecting against pathogenic bacteria, as well as influencing endocrine, neural, humoral, and immunological functions and metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter the gut microbiome, resulting in dysbiosis and microbial dysfunction, which can contribute to a variety of noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, cancer, and irritable bowel syndrome. While most evidence to date is observational and does not establish direct causation, ongoing clinical trials and advanced genomic techniques are steadily enhancing our understanding of these intricate interactions. This review will explore key aspects of the relationship between gut microbiota, eubiosis, and dysbiosis in human health and disease, highlighting emerging strategies for microbiome engineering as potential therapeutic approaches for various conditions.

Childhood obesity is a multifactorial disease affecting more than 160 million adolescents worldwide. Adolescent exposure to obesogenic environments, characterized by access to high-fat diets and stress, precipitates maladaptive eating habits in adulthood such as binge eating. Evidence suggests a strong association between Western-like high-saturated-fat (WD) food consumption and dysregulated hormone fluctuations. However, few studies have explored the long-term impact of adolescent WD and psychosocial stress on brain and behavior. This longitudinal study aimed to investigate the impact of adolescent exposure to an obesogenic diet on stress resiliency and increased susceptibility for binge-like eating behaviors. Adolescent male Lewis rats were given WD (41% fat; n=40) or control diet (CD, 16% fat; n=38) for 4 weeks before undergoing a stress paradigm of predator exposure and social instability (CDE, WDE, CDU, WDU; n=16/group). Subjects were provided intermittent WD access (24 h/week) to evaluate binge eating-like behavior in adulthood. Fecal corticosterone and testosterone were measured at four timepoints throughout adolescence and adulthood. WD rats exhibited increased body weight (p = 0.0217) and elevated testosterone in mid-adolescence (p=0.0312) and blunted stress-induced corticosterone response in mid-late adolescence (CDE:WDE, p=0.028). Adolescent hormone levels were negatively correlated with bingeing and explained the variability between adult rats expressing hyperphagic and hypophagic behaviors. These results demonstrate that exposure to WD in adolescence disrupts hormone fluctuations and stress responsivity, with effects persisting into adulthood. This underscores the importance of addressing obesogenic environments early to mitigate their lasting impact on hormone regulation and stress responsiveness.

Animals' digestion, energy metabolism, and immunity are significantly influenced by interactions between the gut microbiota and the intestinal environment of the host. Previous studies have shown that gut microbiota of Eothenomys miletus can respond to environmental changes, high fiber or fat foods. But how E. miletus in high-altitude adapt to their environment through gut microbiota and physiological changes during winter food shortages period was unclear. In the present study, we evaluated the altitude differences in gut microbiota and their interactions with physiology in terms of body mass regulation in order to study the adaptation of the gut microbiota and physiological indicators of the E. miletus under food restriction settings. E. miletus were collected for this study from Jingdong County (JD, low-altitude) and Xianggelila County (XGLL, high-altitude) in Yunnan Province, China, and split into three groups: control group, food-restricted feeding group for 7 days, and re-feeding group was offered a standard diet for 14 days. 16S rRNA gene sequencing and physiological methods were used to analyze the abundance and community structure of gut microbiota, as well as physiological indicators of each group in E. miletus. The results showed that while the RMR changed more during the period of food restriction, the body mass and major organ masses of E. miletus from high-altitude changed less. After food restriction, RMR in XGLL decreased by 25.25%, while that of in JD decreased by 16.54%. E. miletus from the XGLL had gut bacteria that were more abundant in Firmicutes and had fewer OTUs, and the microbiota had a closer interaction with physiological indicators. Moreover, the gut microbiota adapted to the food shortage environment by enhancing the genera of Bacterroides, Ruminococcus, Turicibacter, and Treponema to improve the utilization of nutrient resources. The interactions between microbial species and the equilibrium of energy homeostasis were further impacted by alterations in physiological indicators and microbial community structure. These variations were important for E. miletus to adapt to the fluctuations and changes of food resources in high-altitude region, which also expand our knowledge of organismal adaptations and the mechanisms behind the interactions between gut bacteria and host physiology.

The intestine is populated by a complex and dynamic assortment of microbes, collectively called gut microbiota, that interact with the host and contribute to its metabolism and physiology. Diet is considered a key regulator of intestinal microbiota, as ingested nutrients interact with and shape the resident microbiota composition. Furthermore, recent studies underscore the interplay of dietary and microbiota-derived nutrients, which directly impinge on intestinal stem cells regulating their turnover to ensure a healthy gut barrier. Although advanced sequencing methodologies have allowed the characterization of the human gut microbiome, mechanistic studies assessing diet-microbiota-host interactions depend on the use of genetically tractable models, such as Drosophila melanogaster. In this review, we first discuss the similarities between the human and fly intestines and then we focus on the effects of diet and microbiota on nutrient-sensing signaling cascades controlling intestinal stem cell self-renewal and differentiation, as well as disease. Finally, we underline the use of the Drosophila model in assessing the role of microbiota in gut-related pathologies and in understanding the mechanisms that mediate different whole-body manifestations of gut dysfunction.

The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.

The purpose of this study is to investigate the effects of non-obese MAFLD on the gut microbiota and metabolic pathways caused by high-temperature processed meals. It was decided to divide the eighteen male Sprague-Dawley rats into three groups: the control group, the dry-fried soybeans (DFS) group, and the high-fat diet (HFD) group. Following the passage of twelve weeks, a series of physical, biochemical, histological, and microbiological examinations were carried out. There were distinct pathological abnormalities brought about by each diet. The DFS diet was found to cause the development of fatty liver and to demonstrate strong relationships between components of the gut microbiota, such as Akkermansia and Mucispirillum, and indices of liver health. Diet-induced changes in the gut microbiome have a significant impact on liver pathology in non-obese patients with metabolically altered liver disease (MAFLD), which suggests that dietary interventions that target gut microbiota could be used to manage or prevent the illness.

Rheumatoid Arthritis (RA) is an autoimmune condition responsible for the impairment of synovia and joints, endangering the functionality of individuals and contributing to mortality. Currently, obesity is increasing worldwide, and recent studies have suggested an association between such condition and RA. In this sense, obese individuals present a lower capacity for achieving remission and present more intense symptoms of the disease, demonstrating a link between both disorders. Different studies aim to understand the possible connection between the conditions; however, few is known in this sense. Therefore, knowing that obesity can alter the activity of multiple body systems, this work's objective is to evaluate the main modifications caused by obesity, which can be linked to the pathophysiology of RA, highlighting as relevant topics obesity's negative impact triggering systemic inflammation, intestinal dysbiosis, endocrine disbalances. Furthermore, the relationship between oxidative stress and obesity also deserves to be highlighted, considering the influence of reactive oxygen species (ROS) accumulation in RA exacerbation. Additionally, many of those characteristics influenced by obesity, along with the classic peculiarities of RA pathophysiology, can also be associated with purinergic signaling. Hence, this work suggests possible connections between the purinergic system and RA, proposing potential therapeutic targets against RA to be studied.

Chronic pain is a heavily debilitating condition and a huge socio-economic burden, with no efficient treatment. Over the past decade, the gut microbiota has emerged as an important regulator of nervous system's health and disease states. Yet, its contribution to the pathogenesis of chronic somatic pain remains poorly documented. Here, we report that male but not female mice lacking Myosin1a (KO) raised under single genotype housing conditions (KO-SGH) are predisposed to develop chronic pain in response to a peripheral tissue injury. We further underscore the potential of MYO1A loss-of-function to alter the composition of the gut microbiota and uncover a functional connection between the vulnerability to chronic pain and the dysbiotic gut microbiota of KO-SGH males. As such, parental antibiotic treatment modifies gut microbiota composition and completely rescues the injury-induced pain chronicity in male KO-SGH offspring. Furthermore, in KO-SGH males, this dysbiosis is accompanied by a transcriptomic activation signature in the dorsal root ganglia (DRG) macrophage compartment, in response to tissue injury. We identify CD206+CD163- and CD206+CD163+ as the main subsets of DRG resident macrophages and show that both are long-lived and self-maintained and exhibit the capacity to monitor the vasculature. Consistently, in vivo depletion of DRG macrophages rescues KO-SGH males from injury-induced chronic pain underscoring a deleterious role for DRG macrophages in a Myo1a-loss-of function context. Together, our findings reveal gene-sex-microbiota interactions in determining the predisposition to injury-induced chronic pain and point-out DRG macrophages as potential effector cells.

Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was "Nutrients" (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research.

Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

Whole-grain foods are rich in bound polyphenols (BPs) whose health benefits were largely underestimated compared with free polyphenols. We first found that DFBP (dietary fiber with BPs from oat bran) exhibited stronger colonic antioxidant activities than DF. 16S rRNA sequencing showed that DFBP selectively changed gut microbial composition, which reciprocally released BPs from DFBP. Released polyphenols from DFBP reduced excessive colonic ROS and exhibited colonic antioxidant activities via the ROS/Akt/Nrf2 pathway revealed by transcriptome and western blot analysis. Colonic antioxidant activities of DFBP mediated by gut microbiota were next proven by treating mice with broad-spectrum antibiotics. Next, Clostridium butyricum, as a distinguished bacterium after DFBP intervention, improved colonic antioxidant capacities synergistically with DFBP in HFD-fed mice. This was explained by the upregulated mRNA expression of esterase, and cellulase of Clostridium butyricum participated in releasing BPs. Our results would provide a solid basis for explaining the health benefits of whole grains.

Exposure to passive heat (acclimation) and exercise under hot conditions (acclimatization), known as heat acclimation (HA), are methods that athletes include in their routines to promote faster recovery and enhance physiological adaptations and performance under hot conditions. Despite the potential positive effects of HA on health and physical performance in the heat, these stimuli can negatively affect gut health, impairing its functionality and contributing to gut dysbiosis. Blood redistribution to active muscles and peripheral vascularization exist during exercise and HA stimulus, promoting intestinal ischemia. Gastrointestinal ischemia can impair intestinal permeability and aggravate systemic endotoxemia in athletes during exercise. Systemic endotoxemia elevates the immune system as an inflammatory responses in athletes, impairing their adaptive capacity to exercise and their HA tolerance. Better gut microbiota health could benefit exercise performance and heat tolerance in athletes. This article suggests that: (1) the intestinal modifications induced by heat stress (HS), leading to dysbiosis and altered intestinal permeability in athletes, can decrease health, and (2) a previously acquired microbial dysbiosis and/or leaky gut condition in the athlete can negatively exacerbate the systemic effects of HA. Maintaining or improving the healthy gut microbiota in athletes can positively regulate the intestinal permeability, reduce endotoxemic levels, and control the systemic inflammatory response. In conclusion, strategies based on positive daily habits (nutrition, probiotics, hydration, chronoregulation, etc.) and preventing microbial dysbiosis can minimize the potentially undesired effects of applying HA, favoring thermotolerance and performance enhancement in athletes.

The influence of gut microbiota in the onset and development of several metabolic diseases has gained attention over the last few years. Diet plays an essential role in gut microbiota modulation. Western diet (WD), characterized by high-sugar and high-fat consumption, alters gut microbiome composition, diversity index, microbial relative levels, and functional pathways. Despite the promising health effects demonstrated by polyunsaturated fatty acids, their impact on gut microbiota is still overlooked. The effect of Fish oil (omega-3 source) and Pomegranate oil (punicic acid source), and a mixture of both oils in gut microbiota modulation were determined by subjecting the oil samples to in vitro fecal fermentations. Cecal samples from rats from two different dietary groups: a control diet (CD) and a high-fat high-sugar diet (WD), were used as fecal inoculum. 16S amplicon metagenomics sequencing showed that Fish oil + Pomegranate oil from the WD group increased α-diversity. This sample can also increase the relative abundance of the Firmicutes and Bacteroidetes phylum as well as Akkermansia and Blautia, which were affected by the WD consumption. All samples were able to increase butyrate and acetate concentration in the WD group. Moreover, tyrosine concentrations, a precursor for dopamine and norepinephrine, increase in the Fish oil + Pomegranate oil WD sample. GABA, an important neurotransmitter, was also increased in WD samples. These results suggest a potential positive impact of these oils' mixture on gut-brain axis modulation. It was demonstrated, for the first time, the great potential of using a mixture of both Fish and Pomegranate oil to restore the gut microbiota changes associated with WD consumption.

The intestinal mucosal barrier-comprising microbial, mechanical, chemical, and immunological barriers-is critical to protection against pathogens and maintenance of host health; however, it remains unclear whether it is affected by environmental contaminants. Therefore, the present study assessed whether exposure to ambient concentrations of nanopolystyrene (NP) and chrysene (CHR)-two ubiquitous environmental pollutants in the aquatic environment-affect the intestinal mucosal barrier in juvenile Siniperca chuatsi. After exposure for 21 days, S. chuatsi exhibited intestinal oxidative stress and imbalance of intestinal microbial homeostasis. NP and/or CHR exposure also disrupted the intestinal mechanical barrier, as evidenced by the altered intestinal epithelial cell morphology, disrupted structure of intercellular tight junctions, and decreased expression of tight junction proteins. Damage to the intestinal chemical barrier manifested as thinning of the mucus layer owing to the loss and damage of goblet cells. Furthermore, the intestinal immunological barrier was impaired as indicated by the loss of intestinal intraepithelial lymphocytes and increase in pro-inflammatory cytokines, chemokines, and immunoglobulins. These findings collectively suggest that the intestinal mucosal barrier was damaged. This study is, to the best of our knowledge, the first to report that exposure to NP and/or CHR at environmentally relevant concentrations disrupts the intestinal mucosal barrier in organisms and highlight the significance of nanoplastic/CHR pollution for intestinal health.

Ligilactobacillus murinus, a member of the Ligilactobacillus genus, holds significant potential as a probiotic. While research on Ligilactobacillus murinus has been relatively limited compared to well-studied probiotic lactic acid bacteria such as Limosilactobacillus reuteri and Lactobacillus gasseri, a mounting body of evidence highlights its extensive involvement in host intestinal metabolism and immune activities. Moreover, its abundance exhibits a close correlation with intestinal health. Notably, beyond the intestinal context, Ligilactobacillus murinus is gaining recognition for its contributions to metabolism and regulation in the oral cavity, lungs, and vagina. As such, Ligilactobacillus murinus emerges as a potential probiotic candidate with a pivotal role in supporting host well-being. This review delves into studies elucidating the multifaceted roles of Ligilactobacillus murinus. It also examines its medicinal potential and associated challenges, underscoring the imperative to delve deeper into unraveling the mechanisms of its actions and exploring its health applications.

Cumulative evidence suggests that intermittent fasting (IF) has beneficial effects on human metabolic health. It has been indicated that its impact on the gut microbiota may mediate these beneficial effects. As a result, we hypothesized that IF may impact the human gut microbiota. A systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol using the PubMed, Scopus, and CINAHL databases. We registered our systematic review protocol in PROSPERO under registration number CRD42021270050. Human intervention studies published until April 30, 2023, were included. The quality of the included studies was assessed using National Institutes of Health (NIH) quality assessment study tools for intervention studies. The search in the database returned 166 studies, of which 13 matched all criteria for the final qualitative analysis. The body of evidence suggests that IF modulates human gut microbiota alpha and beta diversity in lean (relatively healthy) and relatively healthy overweight/obese individuals but not in individuals with metabolic syndrome. Furthermore, IF also alters human gut microbiota composition in all phenotypes. Of interest, the gut microbiota taxa or microbial metabolites after an IF intervention are associated with metabolic markers. According to this review, IF influences the diversity and taxonomic levels of the human gut microbiota. Individual metabolic phenotypes may alter the effect of IF on the diversity and taxonomic levels of the gut microbiota.

Attention toward the preventive effects of postbiotics on metabolic diseases has increased because of greater stability and safety over probiotics. However, studies regarding the bioactive effects of postbiotics, especially from probiotic Bacillus strains, are relatively limited. The anti-obesity effects of the cell-free culture supernatant of Bacillus velezensis KMU01 (CFS-B.vele) were evaluated using high-fat-diet (HFD)-induced mice. HFD-induced mice (n = 8 per group) received equal volumes of (1) CFS-B.vele (114 mg/kg) in PBS, (2) Xenical in PBS, or (3) PBS alone by oral gavage daily for 13 weeks. The results demonstrated that CFS-B.vele changed the gut microbiota and showed anti-obesity effects in HFD-induced obese mice. The elevated Firmicutes/Bacteroidota ratio induced by HFD was decreased in the CFS-B.vele group compared to the other groups (p < 0.05). The CFS-B.vele intervention led to the enrichment of SCFA-producers, such as Roseburia and Eubacterium, in the cecum, suggesting their potential involvement in the amelioration of obesity. Due to these changes, the various obesity-related biomarkers (body weight, fat in tissue, white adipose tissue weight and size, serum LDL-cholesterol level, hepatic lipid accumulation, and adipogenesis/lipogenesis-related gene/protein expression) were improved. Our findings suggest that CFS-B.vele has potential as a novel anti-obesity agent through modulation of the gut microbiota.

Social isolation, a known stressor, can have detrimental effects on both physical and mental health. Recent scientific attention has been drawn to the gut-brain axis, a bidirectional communication system between the central nervous system and gut microbiota, suggesting that gut microbes may influence brain function. This study aimed to explore the impact of social isolation on the intestinal barrier and gut microbiota. 40 male BALB/c mice were either individually housed or kept in groups for 8 and 15 weeks. Socially isolated mice exhibited increased anxiety-like behavior, with significant differences between the 8-week and 15-week isolation groups (P < 0.05). After 8 weeks of isolation, there was a reduction in tight junction protein expression in the intestinal mechanical barrier. Furthermore, after 15 weeks of isolation, both tight junction protein and mucin expression, key components of the intestinal chemical barrier, decreased. This was accompanied by a substantial increase in inflammatory cytokines (IL-6 mRNA, IL-10, and TNF-α) in colon tissue in the 15-week isolated group (P < 0.05). Additionally, Illumina MiSequencing revealed significant alterations in the gut microbiota of socially isolated mice, including reduced Firmicutes and Bacteroides compared to the control group. Lactobacillus levels also decreased in the socially isolated mice.

Kiwifruit pomace, which contains abundant phenolic compounds, is typically discarded during the juicing process, leading to wastage of valuable resources. To address this issue, various indicators (including total acidity, sugar/acid ratio, vitamin C, total polyphenols, polyphenol monomers, and soluble solids content) of 15 kiwifruit cultivars were evaluated and juiced. Then, a polyphenol-concentrated solution from kiwifruit pomace was backfilled into kiwi juice to prepare whole nutritious compound kiwi juice, and its anti-hyperlipidemic activity on obese model mice was then investigated.

Through grey relational analysis and the technique for order preference by similarity to an ideal solution (TOPSIS), Kuimi and Huayou were identified as the predominant varieties for juicing, with weighted relevance scores of 0.695 and 0.871 respectively and TOPSIS scores of 0.6509 and 0.8220 respectively. The polyphenol content of Cuixiang pomace was 43.97 mg g-1 , making it the most suitable choice for polyphenol extraction. By backfilling a polyphenol-concentrated solution derived from Cuixiang pomace into compound kiwi juice of Huayou and Kuimi, the whole nutritious compound kiwi juice with polyphenols was produced and exhibited superior bioactivities, including enhanced hepatic oxidative stress defense, and alleviated serum lipid abnormalities. Furthermore, whole nutritious compound kiwi juice with polyphenols ameliorated host intestinal microbiota dysbiosis by increasing the relative abundance of the phyla Bacteroidota and Verrucomicrobiota.

A hypolipidemic dietary supplement based on kiwifruit pomace polyphenols has been successfully developed, providing an effective solution for hyperlipidemia intervention. © 2023 Society of Chemical Industry.

Compared with the relatively benign effects of increased subcutaneous adipose tissue (SAT), increased visceral adipose tissue (VAT) volume is a causal risk factor for hypertension, hyperlipidemia, type 2 diabetes, and cardiovascular disease. In rodents, increased VAT volume and triglyceride density and ectopic lipid accumulation in kidneys and liver have been induced by alterations in the gut microbiome. However, few studies have characterized these relationships in humans.

To evaluate the tissue triglyceride content of VAT and SAT, liver, kidneys, and pancreas in male and female adults and assess associations with markers of glucose tolerance, serum insulin, and lipids and characteristics of the gut microbiome.

Cross-sectional observational study of healthy human adults (n = 60) at a clinical research center. Body mass index (BMI), body composition, and oral glucose tolerance were assessed. Microbiome analysis was conducted on stool samples using 16S rRNA v3 amplicon sequencing. The triglyceride content of VAT, SAT, liver, kidney and pancreas were determined by assessing proton density fat fraction (PDFF) with magnetic resonance imaging (MRI).

Higher VAT PDFF and the ratio of VAT to SAT PDFF were related to higher BMI, HbA1c, HOMA-IR, non-high-density lipoprotein cholesterol, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, and lower high-density lipoprotein (HDL) cholesterol. A higher VAT PDFF and VAT to SAT PDFF ratio were associated with lower alpha diversity and altered beta diversity of the gut microbiome. Differences in VAT were associated with higher relative abundance of the phylum Firmicutes, lower relative abundance of the phylum Bacteroidetes, and enrichment of the bacterial genera Dorea, Streptococcus, and Solobacterium.

VAT PDFF measured with MRI is related to impaired glucose homeostasis, dyslipidemia, and differences in the gut microbiome, independently of the total body fat percentage.

Microbial protein, produced by fermentation of Fusarium venenatum is a promising candidate alternative protein source. Previous study has demonstrated its ability to improve hyperlipidemia in rats, yet the related mechanism remains unclear. In this study, we aimed to evaluate the potential of F. venenatum as an alternative protein source and its impact on lipid metabolism using multi-omics analysis. Initial experiments with Caenorhabditis elegans revealed that F. venenatum enhanced longevity, improved immune responses, and reduced lipid metabolism by downregulating fat synthesis-related genes. Subsequently, we conducted experiments with mice on a high-fat diet to confirm the anti-obesity effects of F. venenatum. The groups fed F. venenatum showed improved lipid profiles and reduced hepatic fat accumulation. Furthermore, fecal metabolomic analysis showed higher excretion of primary bile acid and cholesterol in the groups fed F. venenatum which might lead to a decrease in lipid digestion and hepatic fat accumulation. Collectively, this series of experiments revealed the potential of F. venenatum as a sustainable alternative protein and its application as an anti-obesity supplement.

Both soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) play pivotal roles in maintaining gut microbiota homeostasis; whether the effects of the different ratios of IDF and SDF are consistent remains unclear. Consequently, we selected SDFs and IDFs from six representative foods (apple, celery, kale, black fungus, oats, and soybeans) and formulated nine dietary fiber recipes composed of IDF and SDF with a ratio from 1 : 9 to 9 : 1 (NDFR) to compare their impact on microbial effects with healthy mice. We discovered that NDFR treatment decreased the abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes at the phylum level. The α diversity and relative richness of Parabacteroides and Prevotella at the genus level showed an upward trend along with the ratio of IDF increasing, while the relative abundance of Akkermansia at the genus level and the production of acetic acid and propionic acid exhibited an increased trend along with the ratio of SDF increasing. The relative abundance of Parabacteroides and Prevotella in the I9S1DF group (the ratio of IDF and SDF was 9 : 1) was 1.72 times and 5.92 times higher than that in the I1S9DF group (the ratio of IDF and SDF was 1 : 9), respectively. The relative abundance of Akkermansia in the I1S9DF group was 17.18 times higher than that in the I9S1DF group. Moreover, a high ratio of SDF (SDF reaches 60% or more) enriched the glycerophospholipid metabolism pathway; however, a high ratio of IDF (IDF reaches 80% or more) regulated the tricarboxylic acid cycle. These findings are helpful in the development of dietary fiber supplements based on gut microbiota and metabolites.

The consumption of probiotics protects pancreatic β-cells from oxidative damage, delaying the onset of type 2 diabetes mellitus (T2DM) and preventing microvascular and macrovascular complications. This study aimed to evaluate the antidiabetic activity of CDE fermented by Lactobacillus casei (ATCC 39539) (LC) in alloxan-induced diabetic rats. The oxidative stress identified by catalase (CAT), serum AST, ALT, ALP, creatinine, urea, and uric acid were measured. The chemical profiles of the plant extract and the fermented extract were studied using HPLC/MS. The potential of the compounds towards the binding pockets of aldose reductase and PPAR was discovered by molecular docking. A significant reduction in fasting blood glucose in alloxan-treated rats. The CAT showed a significant decrease in diabetic rats. Also, serum AST, ALT, ALP, creatinine, urea, and uric acid were significantly decreased in the mixture group. Mild histological changes of pancreatic and kidney tissues suggested that the mixture of probiotics and cleome possesses a marked anti-diabetic effect. Overall, the study suggests that the combination of Cleome droserifolia fermented by Lactobacillus casei exhibits significant antidiabetic activity (p-value=0.05), reduces oxidative stress, improves lipid profiles, and shows potential for the treatment of diabetes.

The prevalence of overweight, obesity, type 2 diabetes, metabolic syndrome and steatotic liver disease is rapidly increasing worldwide with a huge economic burden in terms of morbidity and mortality. Several genetic and environmental factors are involved in the onset and development of metabolic disorders and related complications. A critical role also exists for the gut microbiota, a complex polymicrobial ecology at the interface of the internal and external environment. The gut microbiota contributes to food digestion and transformation, caloric intake, and immune response of the host, keeping the homeostatic control in health. Mechanisms of disease include enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability and translocation of bacterial metabolites which activate a chronic low-grade systemic inflammation and insulin resistance, as precursors of tangible metabolic disorders involving glucose and lipid homeostasis. The ultimate causative role of gut microbiota in this respect remains to be elucidated, as well as the therapeutic value of manipulating the gut microbiota by diet, pre- and pro- synbiotics, or fecal microbial transplantation.

Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.

Land-use change may drive viral spillover from bats into humans, partly through dietary shifts caused by decreased availability of native foods and increased availability of cultivated foods. We manipulated diets of Jamaican fruit bats to investigate whether diet influences shedding of a virus they naturally host. To reflect dietary changes experienced by wild bats during periods of nutritional stress, bats were fed either standard or putative suboptimal diets which were deprived of protein (suboptimal-sugar) and/or supplemented with fat (suboptimal-fat). Upon H18N11 influenza A-virus infection, bats fed the suboptimal-sugar diet shed the most viral RNA for the longest period, but bats fed the suboptimal-fat diet shed the least viral RNA for the shortest period. Unlike mice and humans, bats fed the suboptimal-fat diet displayed higher pre-infection levels of metabolic markers associated with gut health. Diet-driven heterogeneity in viral shedding may influence population-level viral dynamics in wild bats and alter risk of shedding and spillover to humans.

Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer's patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.

In traditional Chinese medicine (TCM), the liver is the "general organ" that is responsible for governing/maintaining the free flow of qi over the entire body and storing blood. According to the classic five elements theory, zang-xiang theory, yin-yang theory, meridians and collaterals theory, and the five-viscera correlation theory, the liver has essential relationships with many extrahepatic organs or tissues, such as the mother-child relationships between the liver and the heart, and the yin-yang and exterior-interior relationships between the liver and the gallbladder. The influences of the liver to the extrahepatic organs or tissues have been well-established when treating the extrahepatic diseases from the perspective of modulating the liver by using the ancient classic prescriptions of TCM and the acupuncture and moxibustion. In modern medicine, as the largest solid organ in the human body, the liver has the typical functions of filtration and storage of blood; metabolism of carbohydrates, fats, proteins, hormones, and foreign chemicals; formation of bile; storage of vitamins and iron; and formation of coagulation factors. The liver also has essential endocrine function, and acts as an immunological organ due to containing the resident immune cells. In the perspective of modern human anatomy, physiology, and pathophysiology, the liver has the organ interactions with the extrahepatic organs or tissues, for example, the gut, pancreas, adipose, skeletal muscle, heart, lung, kidney, brain, spleen, eyes, skin, bone, and sexual organs, through the circulation (including hemodynamics, redox signals, hepatokines, metabolites, and the translocation of microbiota or its products, such as endotoxins), the neural signals, or other forms of pathogenic factors, under normal or diseases status. The organ interactions centered on the liver not only influence the homeostasis of these indicated organs or tissues, but also contribute to the pathogenesis of cardiometabolic diseases (including obesity, type 2 diabetes mellitus, metabolic [dysfunction]-associated fatty liver diseases, and cardio-cerebrovascular diseases), pulmonary diseases, hyperuricemia and gout, chronic kidney disease, and male and female sexual dysfunction. Therefore, based on TCM and modern medicine, the liver has the bidirectional interaction with the extrahepatic organ or tissue, and this established bidirectional interaction system may further interact with another one or more extrahepatic organs/tissues, thus depicting a complex "pan-hepatic network" model. The pan-hepatic network acts as one of the essential mechanisms of homeostasis and the pathogenesis of diseases.

Illegal mining has overshadowed pharmaceutical pollution even though exposure to pharmaceutical waste is high. Consumption of fish potentially polluted with pharmaceuticals from the rivers continues with little concern or potential threat it poses. In the present study, the residues of one antibiotic (Chloramphenicol), five hormones (progesterone, 17-beta Estradiol, Estrone, 17a-Ethynylestradiol, and one), three environmental contaminants (4-para-nonylphenol, 4-tert-octylphenol, and Bisphenol A), one barbiturate (Primidone) and one analgesic (Diclofenac sodium salt), were investigated from fish samples from the rivers Pra, Narkwa, and the Volta. The results show a high concentration of drugs in River Pra in comparison to those in Rivers Narkwa and Volta. The hazard quotients (HQs) for the environmental contaminants were all above 1, except Bisphenol A. Furthermore, the HQs from this study suggest that consumers of fish from any of the three rivers stand a hazard risk of Chloramphenicol (19), 17a-Ethynylestradiol (4), Estrone (1.366), Diclofenac sodium salt (3.29), Progesterone (4.598), 4-tert-octylphenol (87.2), and 4-para-nonylphenol (7.252), but negligible risk against E2 (0.687), Primidone (0.014), Testosterone (0.16), and Bisphenol A (0.642). Of the fish species studied, the highest concentration of all pharmaceuticals put together is found in Clarias gariepinus, Labeo senegalensis, and Chrysichthys nigrodigitatus in that order.

Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with survival. Six-week-old C57BL/6 male mice were randomized to control (non-obese) or high fat diet (obese) for 5-7 weeks. Sepsis was induced by cecal ligation and perforation (CLP). Cytokine levels were measured from cheek bleeds 8 h after CLP, and mice were monitored for survival. Other cohorts were sacrificed 1 h after CLP for plasma and tissue. Septic obese mice had higher survival. At 8 h after sepsis, obese mice had higher adiponectin, leptin, and resistin but lower TNFα and IL-6 compared to non-obese mice. When stratified by 24-h survival, adipokines were not significantly different in obese and non-obese mice. TNFα and IL-6 were higher in non-obese, compared to obese, mice that died within 24 h of sepsis. Diet and to sepsis significantly impacted the cecal microbiome. IL-6 is a prognostic biomarker during early sepsis in non-obese and obese mice. A plausible mechanism for the survival difference in non-obese and obese mice may be the difference in gut microbiome and its evolution during sepsis.

Obesity is closely related to gut microbiota, however, the dynamic change of microbial diversity and composition during the occurrence and development process of obesity is not clear.

A weight-change model of adult Bama pig (2 years, 58 individuals) was established, and weight gain (27 weeks) and weight loss (9 weeks) treatments were implemented. The diversity and community structures of fecal microbiota (418 samples) was investigated by using 16S rRNA (V3-V4) high-throughput sequencing.

During the weight gain period (1~27 week), the alpha diversity of fecal microbiota exhibited a "down-up-down" fluctuations, initially decreasing, recovering in the mid-term, and decreasing again in the later stage. Beta diversity also significantly changed over time, indicating a gradual deviation of the microbiota composition from the initial time point. Bacteroides, Clostridium sensu stricto 1, and Escherichia-Shigella showed positive correlations with weight gain, while Streptococcus, Oscillospira, and Prevotellaceae UCG-001 exhibited negative correlations. In the weight loss period (30~38 week), the alpha diversity further decreased, and the composition structure underwent significant changes compared to the weight gain period. Christensenellaceae R-7 group demonstrated a significant increase during weight loss and showed a negative correlation with body weight. Porphyromonas and Campylobacter were positively correlated with weight loss.

Both long-term fattening and weight loss induced by starvation led to substantial alterations in porcine gut microbiota, and the microbiota changes observed during weight gain could not be recovered during weight loss. This work provides valuable resources for both obesity-related research of human and microbiota of pigs.

Dietary fiber is a carbohydrate polymer with ten or more monomeric units that are resistant to digestion by human digestive enzymes, and it has gained widespread attention due to its significant role in health improvement through regulating gut microbiota. In this review, we summarized the interaction between dietary fiber, gut microbiota, and obesity, and the beneficial effects of dietary fiber on obesity through the modulation of microbiota, such as modifying selective microbial composition, producing starch-degrading enzymes, improving gut barrier function, reducing the inflammatory response, reducing trimethylamine N-oxide, and promoting the production of gut microbial metabolites (e.g., short chain fatty acids, bile acids, ferulic acid, and succinate). In addition, factors affecting the gut microbiota composition and metabolites by dietary fiber (length of the chain, monosaccharide composition, glycosidic bonds) were also concluded. Moreover, strategies for enhancing the biological activity of dietary fiber (fermentation technology, ultrasonic modification, nanotechnology, and microfluidization) were subsequently discussed. This review may provide clues for deeply exploring the structure-activity relationship between dietary fiber and antiobesity properties by targeting specific gut microbiota.

Gut microbiota influence host immunity and metabolism during obesity. Bacterial sensors of the innate immune system relay signals from specific bacterial components (i.e., postbiotics) that can have opposing outcomes on host metabolic inflammation. NOD-like receptors (NLRs) such as Nod1 and Nod2 both recruit receptor-interacting protein kinase 2 (RIPK2) but have opposite effects on blood glucose control. Nod1 connects bacterial cell wall-derived signals to metabolic inflammation and insulin resistance, whereas Nod2 can promote immune tolerance, insulin sensitivity, and better blood glucose control during obesity. NLR family pyrin domain containing (NLRP) inflammasomes can also generate divergent metabolic outcomes. NLRP1 protects against obesity and metabolic inflammation potentially because of a bias toward IL-18 regulation, whereas NLRP3 appears to have a bias toward IL-1β-mediated metabolic inflammation and insulin resistance. Targeting specific postbiotics that improve immunometabolism is a key goal. The Nod2 ligand, muramyl dipeptide (MDP) is a short-acting insulin sensitizer during obesity or during inflammatory lipopolysaccharide (LPS) stress. LPS with underacylated lipid-A antagonizes TLR4 and counteracts the metabolic effects of inflammatory LPS. Providing underacylated LPS derived from Rhodobacter sphaeroides improved insulin sensitivity in obese mice. Therefore, certain types of LPS can generate metabolically beneficial metabolic endotoxemia. Engaging protective adaptive immunoglobulin immune responses can also improve blood glucose during obesity. A bacterial vaccine approach using an extract of the entire bacterial community in the upper gut promotes protective adaptive immune response and long-lasting improvements in blood glucose control. A key future goal is to identify and combine postbiotics that cooperate to improve blood glucose control.

Obesity and metabolic comorbidities are associated with gut permeability. While high-fructose and Western-style diet (WSD) disrupt intestinal barrier function, oral administration of human α-defensin 5 (HD5) and β-defensin 2 (hBD2) is believed to improve intestinal integrity and metabolic disorders. Eighty-four male C57BL/6J mice were fed a WSD or a control diet (CD) ± fructose (F) for 18 weeks. In week 13, mice were randomly divided into three intervention groups, receiving defensin fragment HD51-9, full-length hBD2, or bovine serum albumin (BSA)-control for six weeks. Subsequently, parameters of hepatic steatosis, glucose metabolism, and gut barrier function were assessed. WSDF increased body weight and hepatic steatosis (p < 0.01) compared to CD-fed mice, whereas peptide intervention decreased liver fat (p < 0.05) and number of hepatic lipid droplets (p < 0.01) compared to BSA-control. In addition, both peptides attenuated glucose intolerance by reducing blood glucose curves in WSDF-fed mice. Evaluation of gut barrier function revealed that HD51-9 and hBD2 improve intestinal integrity by upregulating tight junction and mucin expression. Moreover, peptide treatment restored ileal host defense peptides (HDP) expression, likely by modulating the Wnt, Myd88, p38, and Jak/STAT pathways. These findings strongly suggest that α- and β-defensin treatment improve hepatic steatosis, glucose metabolism, and gut barrier function.