High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity.
Ontology highlight
ABSTRACT:
SUBMITTER: Rizvi ZA
PROVIDER: S-EPMC8442882 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.
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Project description:Emerging data indicate a correlation between gut microbial composition and cardiovascular disease including hypertension. The host's diet greatly affects microbial composition and metabolite production. Short chain fatty acids (SCFAs) are products of microbial fermentation, which can be utilized by the host. It has been suggested that SCFAs play a pivotal role as mediators in a microbiome host: microbial interactions occur in health and disease. The aim of this study was to evaluate the effect of a high salt diet (HSD) on microbial variation and to determine whether this effect is accompanied by an alteration in fecal SCFAs. To this end, Dahl salt-sensitive rats were divided into two groups (n = 10 each): (A) Control: fed regular chow; and (B) Fed HSD. High-throughput pyrosequencing of the 16S rRNA amplicon sequencing was used for microbiome characterizing. Chromatography-mass spectrometry was used to measure the levels of SCFAs: acetic acid, propionic acid, butyric acid, and isobutyric acid in fecal samples. Differences in microbial composition were noted between groups. Principal Coordinate Analysis (PCoA) principal coordinate 1 (PC1) primarily separated controls from the HSD. Four taxa displayed significant differences between HSD and controls. Taxa from the Erwinia genus, the Christensenellaceae and Corynebacteriaceae families, displayed an increased abundance in HSD versus control. In contrast, taxa from the Anaerostipes genus displayed a decreased abundance in HSD. We were able to identify seven unique taxa that were significantly associated with blood pressure. There was a significant difference in fecal acetic acid, as well as propionic and isobutyric acid, but not in the butyric acid composition between groups. Adding salt to a diet impacts the gut's microbial composition, which may alter fecal SCFA production.
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Project description:The gut microbiome has been implicated in polycystic ovary syndrome (PCOS) pathophysiology. PCOS is a disorder with reproductive, endocrine and metabolic irregularities, and several studies report that PCOS is associated with a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, as alterations in macronutrient composition impact the balance of gut microbial communities. This study investigated the interplay between macronutrient balance and PCOS on the gut microbiome of control and dihydrotestosterone (DHT)-induced PCOS-like mice exposed to diets that varied in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha (α) and beta (β) diversity of the gut microbiota of control and PCOS-like mice. However, α-diversity between control and PCOS-like mice on the same diet did not differ significantly. In contrast, β-diversity was significantly altered by PCOS pathology. Further analysis identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) with 99.2% similarity to Bacteroides acidifaciens, which is inversely associated with obesity, to be significantly decreased in PCOS-like mice. Additionally, this study investigated the role of the gut microbiome in the development of PCOS traits, whereby PCOS-like mice were transplanted with healthy fecal microbiota from control mice. Although the PCOS gut microbiome shifted toward that of control mice, PCOS traits were not ameliorated. Overall, these findings demonstrate that while diet exerts a stronger influence over gut microbiota diversity than PCOS pathology, overall gut microbiota composition is affected by PCOS pathology.
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Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression.
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Project description:The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-γ expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-γ expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases.
| S-EPMC8966992 | biostudies-literature
Project description:The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes. First, faecal and salivary samples were collected from periodontally healthy participants (PH group, n = 16) and patients with severe periodontitis (SP group, n = 21) and analysed by 16S ribosomal RNA sequencing. Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups. Notably, more saliva-sourced microbes were observed in the faecal samples of the SP group. Then, the remaining salivary microbes were transplanted into C57BL6/J mice (the C-PH group and the C-SP group), and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group, with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group. In the colon, the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression. The mRNA expression levels of pro-inflammatory cytokines, chemokines and tight junction proteins were significantly higher in the C-SP group. To further investigate whether salivary bacteria could persist in the intestine, the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice. We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h. Thus, our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.
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Project description:Central to the understanding of the relationships between diet, gut microbiota, and vitamins D and A in multiple sclerosis is low-grade inflammation, which is involved in all chronic inflammatory diseases and is influenced by each of the above effectors. We show that food components have either proinflammatory or anti-inflammatory effects and influence both the human metabolism (the "metabolome") and the composition of gut microbiota. Hypercaloric, high-animal-fat Western diets favor anabolism and change gut microbiota composition towards dysbiosis. Subsequent intestinal inflammation leads to leakage of the gut barrier, disruption of the blood-brain barrier, and neuroinflammation. Conversely, a vegetarian diet, rich in fiber, is coherent with gut eubiosis and a healthy condition. Vitamin D levels, mainly insufficient in a persistent low-grade inflammatory status, can be restored to optimal values only by administration of high amounts of cholecalciferol. At its optimal values (>30 ng/ml), vitamin D requires vitamin A for the binding to the vitamin D receptor and exert its anti-inflammatory action. Both vitamins must be supplied to the subjects lacking vitamin D. We conclude that nutrients, including the nondigestible dietary fibers, have a leading role in tackling the low-grade inflammation associated with chronic inflammatory diseases. Their action is mediated by gut microbiota and any microbial change induced by diet modifies host-microbe interactions in a consequent way, to improve the disease or worsen it.
| S-EPMC5794694 | biostudies-other
Project description:IntroductionMaternal obesity poses risks for both mother and offspring during pregnancy, with underlying mechanisms remaining largely unexplored. Obesity is associated with microbial gut dysbiosis and low-grade inflammation, and also the diet has a major impact on these parameters. This study aimed to investigate how maternal obesity and diet contribute to changes in immune responses, exploring potential associations with gut microbiota dysbiosis and adverse pregnancy outcomes in mice.MethodsBefore mating, C57BL/6 mice were assigned to either a high-fat-diet (HFD) or low-fat-diet (LFD) to obtain obese (n=17) and lean (n=10) mice. To distinguish between the effects of obesity and diet, 7 obese mice were switched from the HFD to the LFD from day 7 until day 18 of pregnancy ("switch group"), which was the endpoint of the study. T helper (Th) cell subsets were studied in the spleen, mesenteric lymph nodes (MLN) and Peyer's patches (PP), while monocyte subsets and activation status were determined in maternal blood (flow cytometry). Feces were collected before and during pregnancy (day 7,14,18) for microbiota analysis (16S rRNA sequencing). Pregnancy outcome included determination of fetal and placental weight.ResultsObesity increased splenic Th1 and regulatory T cells, MLN Th1 and PP Th17 cells and enhanced IFN-γ and IL-17A production by splenic Th cells upon ex vivo stimulation. Switching diet decreased splenic and PP Th2 cells and classical monocytes, increased intermediate monocytes and activation of intermediate/nonclassical monocytes. Obesity and diet independently induced changes in the gut microbiota. Various bacterial genera were increased or decreased by obesity or the diet switch. These changes correlated with the immunological changes. Fetal weight was lower in the obese than the lean group, while placental weight was lower in the switch than the obese group.DiscussionThis study demonstrates that obesity and diet independently impact peripheral and intestinal immune responses at the end of pregnancy. Simultaneously, both factors affect specific bacterial gut genera and lead to reduced fetal or placental weight. Our data suggest that switching diet during pregnancy to improve maternal health is not advisable and it supports pre/probiotic treatment of maternal obesity-induced gut dysbiosis to improve maternal immune responses and pregnancy outcome.
| S-EPMC11272480 | biostudies-literature
Project description:A high-salt diet (HSD) elicits sustained sterile inflammation and worsens tissue injury. However, how this occurs after stroke, a leading cause of morbidity and mortality, remains unknown. Here, we report that HSD impairs long-term brain recovery after intracerebral hemorrhage, a severe form of stroke, despite salt withdrawal prior to the injury. Mechanistically, HSD induces innate immune priming and training in hematopoietic stem and progenitor cells (HSPCs) by downregulation of NR4a family and mitochondrial oxidative phosphorylation. This training compromises alternative activation of monocyte-derived macrophages (MDMs) without altering the initial inflammatory responses of the stroke brain. Healthy mice transplanted with bone marrow from HSD-fed mice retain signatures of reduced MDM reparative functions, further confirming a persistent form of innate immune memory that originates in the bone marrow. Loss of NR4a1 in macrophages recapitulates HSD-induced negative impacts on stroke outcomes while gain of NR4a1 enables stroke recovery in HSD animals. Together, we provide the first evidence that links HSD-induced innate immune memory to the acquisition of persistent dysregulated inflammatory responses and unveils NR4a1 as a potential therapeutic target.
| S-SCDT-10_15252-EMBR_202357164 | biostudies-other