n-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in Mycobacterium tuberculosis-infected C3HeB/FeJ mice, dependent on fatty acid status.

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection. Using a two-by-two design, uninfected mice were conditioned on either an n-3 PUFA-sufficient (n-3FAS) or -deficient (n-3FAD) diet for 6 weeks. One week post-infection, mice were randomised to either n-3 LCPUFA supplemented (n-3FAS/n-3+ and n-3FAD/n-3+) or continued on n-3FAS or n-3FAD diets for 3 weeks. Mice were euthanised and fatty acid status, lung bacterial load and pathology, cytokine, lipid mediator and immune cell phenotype analysed. n-3 LCPUFA supplementation in n-3FAS mice lowered lung bacterial loads (P = 0·003), T cells (P = 0·019), CD4+ T cells (P = 0·014) and interferon (IFN)-γ (P < 0·001) and promoted a pro-resolving lung lipid mediator profile. Compared with n-3FAS mice, the n-3FAD group had lower bacterial loads (P = 0·037), significantly higher immune cell recruitment and a more pro-inflammatory lipid mediator profile, however, significantly lower lung IFN-γ, IL-1α, IL-1ß and IL-17, and supplementation in the n-3FAD group provided no beneficial effect on lung bacterial load or inflammation. Our study provides the first evidence that n-3 LCPUFA supplementation has antibacterial and inflammation-resolving benefits in TB when provided 1 week after infection in the context of a sufficient n-3 PUFA status, whilst a low n-3 PUFA status may promote better bacterial control and lower lung inflammation not benefiting from n-3 LCPUFA supplementation.

Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation.

The inflammatory effects of carrageenan (CGN), a ubiquitous food additive, remains controversial. Gut microbiota and intestinal homeostasis may be a breakthrough in resolving this controversy. Here we show that, κ-CGN did not cause significant inflammatory symptoms, but it did cause reduced bacteria-derived short-chain fatty acids (SCFAs) and decreased thickness of the mucus layer by altering microbiota composition. Administration of the pathogenic bacterium Citrobacter rodentium, further aggravated the inflammation and mucosal damage in the presence of κ-CGN. Mucus layer degradation and altered SCFA levels could be reproduced by fecal transplantation from κ-CGN-fed mice, but not from germ-free κ-CGN-fed mice. These symptoms could be partially repaired by administering probiotics. Our results suggest that κ-CGN may not be directly inflammatory, but it creates an environment that favors inflammation by perturbation of gut microbiota composition and then facilitates expansion of pathogens, and this effect may be partially reversed by the introduction of probiotics.

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin.

Because of a possible impact of capsaicin in the high concentrations on enterocyte injury (cytotoxicity) and bactericidal activity on probiotics, Lactobacillus rhamnosus L34 (L34) and Lactobacillus rhamnosus GG (LGG), the probiotics derived from Thai and Caucasian population, respectively, were tested in the chili-extract administered C57BL/6 mice and in vitro experiments. In comparison with placebo, 2 weeks administration of the extract from Thai chili in mice caused loose feces and induced intestinal permeability defect as indicated by FITC-dextran assay and the reduction in tight junction molecules (occludin and zona occludens-1) using fluorescent staining and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the chili extracts also induced the translocation of gut pathogen molecules; lipopolysaccharide (LPS) and (1→3)-ß-d-glucan (BG) and fecal dysbiosis (microbiome analysis), including reduced Firmicutes, increased Bacteroides, and enhanced total Gram-negative bacteria in feces. Both L34 and LGG attenuated gut barrier defect (FITC-dextran, the fluorescent staining and gene expression of tight junction molecules) but not improved fecal consistency. Additionally, high concentrations of capsaicin (0.02-2 mM) damage enterocytes (Caco-2 and HT-29) as indicated by cell viability test, supernatant cytokine (IL-8), transepithelial electrical resistance (TEER) and transepithelial FITC-dextran (4.4 kDa) but were attenuated by Lactobacillus condition media (LCM) from both probiotic-strains. The 24 h incubation with 2 mM capsaicin (but not the lower concentrations) reduced the abundance of LGG (but not L34) implying a higher capsaicin tolerance of L34. However, Lactobacillus rhamnosus fecal abundance, using qRT-PCR, of L34 or LGG after 3, 7, and 20 days of the administration in the Thai healthy volunteers demonstrated the similarity between both strains. In conclusion, high dose chili extracts impaired gut permeability and induced gut dysbiosis but were attenuated by probiotics. Despite a better capsaicin tolerance of L34 compared with LGG in vitro, L34 abundance in feces was not different to LGG in the healthy volunteers. More studies on probiotics with a higher intake of chili in human are interesting.

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4 -Induced Hepatic Fibrosis by Modulating Gut Microbiota.

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl4 -induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl4 -induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl4 -induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl4 -induced hepatic fibrosis.

Ferritin H deficiency deteriorates cellular iron handling and worsens Salmonella typhimurium infection by triggering hyperinflammation.

Iron is an essential nutrient for mammals as well as for pathogens. Inflammation-driven changes in systemic and cellular iron homeostasis are central for host-mediated antimicrobial strategies. Here, we studied the role of the iron storage protein ferritin H (FTH) for the control of infections with the intracellular pathogen Salmonella enterica serovar Typhimurium by macrophages. Mice lacking FTH in the myeloid lineage (LysM-Cre+/+Fthfl/fl mice) displayed impaired iron storage capacities in the tissue leukocyte compartment, increased levels of labile iron in macrophages, and an accelerated macrophage-mediated iron turnover. While under steady-state conditions, LysM-Cre+/+Fth+/+ and LysM-Cre+/+Fthfl/fl animals showed comparable susceptibility to Salmonella infection, i.v. iron supplementation drastically shortened survival of LysM-Cre+/+Fthfl/fl mice. Mechanistically, these animals displayed increased bacterial burden, which contributed to uncontrolled triggering of NF-κB and inflammasome signaling and development of cytokine storm and death. Importantly, pharmacologic inhibition of the inflammasome and IL-1ß pathways reduced cytokine levels and mortality and partly restored infection control in iron-treated ferritin-deficient mice. These findings uncover incompletely characterized roles of ferritin and cellular iron turnover in myeloid cells in controlling bacterial spread and for modulating NF-κB and inflammasome-mediated cytokine activation, which may be of vital importance in iron-overloaded individuals suffering from severe infections and sepsis.

Mechanism underlying Polygonum capitatum effect on Helicobacter pylori-associated gastritis based on network pharmacology.

Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori-associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment.

Metabolomics-Guided Hypothesis Generation for Mechanisms of Intestinal Protection by Live Biotherapeutic Products.

The use of live biotherapeutic products (LBPs), including single strains of beneficial probiotic bacteria or consortiums, is gaining traction as a viable option to treat inflammatory-mediated diseases like inflammatory bowel disease (IBD). However, LBPs' persistence in the intestine is heterogeneous since many beneficial bacteria lack mechanisms to tolerate the inflammation and the oxidative stress associated with IBD. We rationalized that optimizing LBPs with enhanced colonization and persistence in the inflamed intestine would help beneficial bacteria increase their bioavailability and sustain their beneficial responses. Our lab developed two bioengineered LBPs (SBT001/BioPersist and SBT002/BioColoniz) modified to enhance colonization or persistence in the inflamed intestine. In this study, we examined colon-derived metabolites via ultra-high performance liquid chromatography-mass spectrometry in colitic mice treated with either BioPersist or BioColoniz as compared to their unmodified parent strains (Escherichia coli Nissle 1917 [EcN] and Lactobacillus reuteri, respectively) or to each other. BioPersist administration resulted in lowered concentrations of inflammatory prostaglandins, decreased stress hormones such as adrenaline and corticosterone, increased serotonin, and decreased bile acid in comparison to EcN. In comparison to BioColoniz, BioPersist increased serotonin and antioxidant production, limited bile acid accumulation, and enhanced tissue restoration via activated purine and pyrimidine metabolism. These data generated several novel hypotheses for the beneficial roles that LBPs may play during colitis.

A Role for Folate in Microbiome-Linked Control of Autoimmunity.

The microbiome exerts considerable control over immune homeostasis and influences susceptibility to autoimmune and autoinflammatory disease (AD/AID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis, and uveitis. In part, this is due to direct effects of the microbiome on gastrointestinal (GI) physiology and nutrient transport, but also to indirect effects on immunoregulatory controls, including induction and stabilization of T regulatory cells (T reg). Secreted bacterial metabolites such as short-chain fatty acids (SCFA) are under intense investigation as mediators of these effects. In contrast, folate (vitamin B9), an essential micronutrient, has attracted less attention, possibly because it exerts global physiological effects which are difficult to differentiate from specific effects on the immune system. Here, we review the role of folate in AD/AID with some emphasis on sight-threatening autoimmune uveitis. Since folate is required for the generation and maintenance of T reg , we propose that one mechanism for microbiome-based control of AD/AID is via folate-dependent induction of GI tract T reg , particularly colonic T reg, via anergic T cells (T an). Hence, folate supplementation has potential prophylactic and/or therapeutic benefit in AID/AD.

Gastrodia remodels intestinal microflora to suppress inflammation in mice with early atherosclerosis.

Atherosclsis is a critical actuator causing cardiac-cerebral vascular disease with a complicated pathogeneon, refered to the disorders of intestinal flora and persistent inflammation. Gastrodin (4-(hydroxymethyl) phenyl-ß-D- Glucopyranoside) is the most abundant glucoside extracted from the Gastrodiaelata, which is a traditional Chinese herbal medicine for cardiac-cerebral vascular disease, yet its mechanisms remain little known. In the present study, the gastrodia extract and gastrodin attenuate the lipid deposition and foam cells on the inner membrane of the inner membrane of the thoracic aorta in the early atherosclerosis mice. Blood lipid detection tips that TC and LDL-C were reduced in peripheral blood after treatment with the gastrodia extract and gastrodin. Furthermore, unordered gut microbes are remodeled in terms of bacterial diversity and abundance at family and genus level. Also, the intestinal mucosa damage and permeability were reversed, accompaniedwith the reducing of inflammatory cytokines. Our findings revealed that the functions of gastrodia extract and gastrodin in cardiac-cerebral vascular disease involved to rescued gut microbes and anti-inflammation may be the mechanismof remission lipid accumulation.

Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model.

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

Brazilian Red Propolis shows antifungal and immunomodulatory activities against Paracoccidioides brasiliensis.

ETHNOPHARMACOLOGICAL RELEVANCE: Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in South America and especially in Brazil with severe clinical consequences that need broadened therapeutic options. Propolis is a natural resin from bees used in folk medicine for centuries with the first report in the ancient history of Egypt by Eberly papyrus, in Middle-Ages used to wash the newborn's umbilical cord and World War II as antiseptic or antibiotics. Nowadays it is a natural product worldwide consumed as food and traditionally used for oral and systemic diseases as an anti-inflammatory, antimicrobial, antifungal, and other diseases. Brazilian red propolis (BRP) is a new type of propolis with a distinguished chemical profile and biological activities from propolis (green) with pharmacological properties such as antimicrobial, anti-inflammatory, antioxidant, and others. AIM OF STUDY: Thus, the main purpose of this study was to investigate the direct in vitro and ex vivo effect of BRP on Paracoccidioides brasiliensis. MATERIAL AND METHODS: Antifungal activity of different concentrations of BRP on a virulent P. brasiliensis isolate (Pb18) was evaluated using the microdilution technique. Also, mice splenic cells co-cultured with Pb18 were treated with BRP at different times and concentrations (only Pb18 = negative control). Mice were inoculated with Pb18 and treated with different concentrations of BRP (50-500 mg/mL) in a subcutaneous air pouch. In this later experimental model, macroscopic characteristics of the air pouch were evaluated, and cellular exudate was collected and analyzed for cellular composition, mitochondrial activity, total protein reactive oxygen specimens (ROS), and nitric oxide production, as well as the number of viable fungal cells. RESULTS: The in vitro experiments showed remarkable direct antifungal activity of BRP, mainly with the highest concentration employed (500 mg/mL), reducing the number of viable cells to 10% of the original inoculum after 72 h incubation. The splenocytes co-cultivation assays showed that BRP had no cytotoxic effect on these cells, on the contrary, exerted a stimulatory effect. This stimulation was also observed on the PMNs at the air pouch, as verified by production of ROS and total proteins and mitochondrial activity. This activation resulted in enhanced fungicidal activity, mainly with the 500 mg/mL concentration of BRP. An anti-inflammatory effect was also detected, as verified by the smaller volume of the BRP-treated air pouch as well as by an earlier shift from neutrophils to mononuclear cells present in the infection site. CONCLUSION: Our results strongly suggest, for the first time in the literature, that Brazilian Red propolis has four protective mechanisms in experimental paracoccidioidomycosis: activating neutrophils, exerting a direct antifungal effect, preventing fungal dissemination, and controlling excessive inflammation process.

Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation.

Gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut-liver cross talk in nonalcoholic fatty liver disease (NAFLD). Lycium barbarum polysaccharides (LBPs), which seem to be a potential prebiotic, and aerobic exercise (AE) have shown protective effects on NAFLD. However, their combined effects on intestinal microecology remain unclear. This study evaluated the effects of LBP, AE, and its combination (LBP + AE) on gut microbiota composition, intestinal barrier, and hepatic inflammation in NAFLD. LBP + AE showed high abundance and diversity of gut microbiota, restored the gut microbiota composition, increased some Bacteroidetes, short chain fatty acids, but decreased Proteobacteria and the ratio of Firmicutes/Bacteroidetes. Simultaneously, LBP, AE, and LBP + AE could restore the colonic and ileum tight junctions by increasing the expression of zonula occludens-1 and occludin. They also downregulated gut-derived lipopolysaccharides (LPSs), hepatic LPS-binding proteins, inflammatory factors, and related indicators of the LPS/TLR4/NF-κB signaling pathway for the liver. Our results implied that LBP could be considered a prebiotic agent, and LBP + AE might be a promising treatment for NAFLD because it could maintain gut microbiota balance, thereby restoring intestinal barrier and exerting hepatic benefits.

Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation.

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg-1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1ß) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.

Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease.

Clostridium butyricum is a butyrate-producing human gut symbiont that has been safely used as a probiotic for decades. C. butyricum strains have been investigated for potential protective or ameliorative effects in a wide range of human diseases, including gut-acquired infection, intestinal injury, irritable bowel syndrome, inflammatory bowel disease, neurodegenerative disease, metabolic disease, and colorectal cancer. In this review we summarize the studies on C. butyricum supplementation with special attention to proposed mechanisms for the associated health benefits and the supporting experimental evidence. These mechanisms center on molecular signals (especially butyrate) as well as immunological signals in the digestive system that cascade well beyond the gut to the liver, adipose tissue, brain, and more. The safety of probiotic C. butyricum strains appears well-established. We identify areas where additional human randomized controlled trials would provide valuable further data related to the strains' utility as an intervention.

Protective effects of Re-yan-ning mixture on Streptococcus pneumonia in rats based on network pharmacology.

CONTEXT: Re-yan-ning mixture (RYNM) is a new national drug approved by China's State Food and Drug Administration for the treatment of colds, simple pneumonia and acute bronchitis. OBJECTIVE: To determine the mechanism of action of RYNM in the treatment of bacterial pneumonia. MATERIALS AND METHODS: Using the network pharmacology approach, the multiple components, component candidate targets and multiple therapeutic targets of RYNM were screened and functionally enriched. Also, we established a rat Streptococcus pneumonia model to verify the results of network pharmacology enrichment analysis. Forty male SPF Sprague Dawley rats were divided into four groups of 10 rats: control (normal saline), model (normal saline), levofloxacin-intervened and RYNM-intervened groups. IL-10, NOS2, COX-1, IL-6, TNF-α and NF-κB in serum and BALF were detected by ELISA. Western blot detected IL-17, IL-6, TNF-α, COX-2 and Bcl-2. RESULTS: The network pharmacology approach successfully identified 48 bioactive components in RYNM, and 65 potential targets and 138 signal pathways involved in the treatment of Streptococcus pneumonia with RYNM. The in vivo experiments indicated that model group has visible inflammation and lesions while RYNM and levofloxacin groups have not. The RYNM exhibited its therapeutic effects on Streptococcus pneumonia mainly via the regulation of cell proliferation and survival through the IL-6/IL-10/IL-17, Bax/Bcl-2, COX-1/COX-2, NF-κB and TNF-α signalling pathways. DISCUSSION AND CONCLUSIONS: The present study demonstrated the protective effects of RYNM on Streptococcus pneumonia, providing a potential mechanism for the treatment of bacterial pneumonia with RYNM.

Suppressive Effect of Two Cucurbitane-Type Triterpenoids from Momordica charantia on Cutibacterium acnes-Induced Inflammatory Responses in Human THP-1 Monocytic Cell and Mouse Models.

Cutibacterium acnes (formerly Propionibacterium acnes) is one of the major bacterial species responsible for acne vulgaris. Numerous bioactive compounds from Momordica charantia Linn. var. abbreviata Ser. have been isolated and examined for many years. In this study, we evaluated the suppressive effect of two cucurbitane-type triterpenoids, 5ß,19-epoxycucurbita-6,23-dien-3ß,19,25-triol (Kuguacin R; KR) and 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD) on live C. acnes-stimulated in vitro and in vivo inflammatory responses. Using human THP-1 monocytes, KR or TCD suppressed C. acnes-induced production of interleukin (IL)-1ß, IL-6 and IL-8 at least above 56% or 45%, as well as gene expression of these three pro-inflammatory cytokines. However, a significantly strong inhibitory effect on production and expression of tumor necrosis factor (TNF)-α was not observed. Both cucurbitanes inhibited C. acnes-induced activation of the myeloid differentiation primary response 88 (MyD88) (up to 62%) and mitogen-activated protein kinases (MAPK) (at least 36%). Furthermore, TCD suppressed the expression of pro-caspase-1 and cleaved caspase-1 (p10). In a separate study, KR or TCD decreased C. acnes-stimulated mouse ear edema by ear thickness (20% or 14%), and reduced IL-1ß-expressing leukocytes and neutrophils in mouse ears. We demonstrated that KR and TCD are potential anti-inflammatory agents for modulating C. acnes-induced inflammation in vitro and in vivo.

Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Despite advances in research on type 2 diabetes mellitus (T2DM) with the development of science and technology, the pathogenesis and treatment response of T2DM remain unclear. Recent studies have revealed a significant role of the microbiomein the development of T2DM, and studies have found that the gut microbiota may explain the therapeutic effect of traditional Chinese medicine (TCM), a primary branch of alternative and complementary medicine, in the treatment of T2DM. The aim of this study was to systematically review all randomized controlled trials (RCTs) on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients. METHODS: All RCTs investigating the effects of TCM interventions on modulating gut microbiota and improving glucose metabolism in the treatment of T2DM adults were included. Meta-analyses were conducted when sufficient data were available, other results were reported narratively. The study protocol was pre-specified, documented, and published in PROSPERO (registration no. CRD42020188043). RESULTS: Five studies met the eligibility criteria ofthe systematic review. All five studies reported the effects of TCM interventions on the gut microbiota modulation and blood glucose control. There were statistically significant improvements in HbA1c (mean difference [MD]: -0.69%; [95% CI -0.24, -0.14]; p = 0.01, I2 = 86%), fasting blood glucose (MD: -0.87 mmol/l; [95% CI -1.26, -0.49]; p < 0.00001, I2 = 75%) and 2-h postprandial blood glucose(MD: -0.83mmol/l; [95% CI: -1.01, -0.65]; p < 0.00001, I2 = 0%). In addition, there were also statistically significant improvements in homeostasis model assessment of insulin resistance (HOMA-IR) (standardized mean difference [SMD]: -0.99, [95% CI -1.25 to -0.73]; p < 0.00001, I2 = 0%) and homeostasis model assessment of ß-cell function (HOMA-ß) (SMD: 0.54, [95% CI 0.21 to 0.87]; p = 0.001, I2 = 0%).There was a significant change in the relative abundance of bacteria in the genera Bacteroides (standardized mean difference [SMD] 0.87%; [95% CI 0.58, 1.16], however, the change in Enterococcus abundance was not statistically significant (SMD: -1.71%; [95% CI: -3.64, 0.23]; p = 0.08) when comparing TCM supplementaltreatment with comparator groups. Other changes in the gut microbiota, including changes in the relative abundances of some probiotics and opportunistic pathogens at various taxon levels, and changes in diversity matrices (α and ß), were significant by narrative analysis. However, insufficient evidences were found to support that TCM intervention had an effect on inflammation. CONCLUSION: TCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients. Although the results of the included studies are encouraging, further well-conducted studies on TCM interventions targeting the gut microbiota are needed.

Variation in essential oil components and anti-inflammatory activity of Allophylus edulis leaves collected in central-western Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: An infusion obtained from the leaves of "chal-chal" (Allophylus edulis Radlk.) is used for popular treatment of intestinal disorders and as an anti-inflammatory throat treatment. Because of the anti-inflammatory medicinal folk use, a previous work reported scientific research confirming the anti-inflammatory activity of A. edulis essential oil collected in Dourados, MS, Brazil, in March 2015. AIM OF THE STUDY: The aim of this study was to evaluate the variation in the chemical profile of the essential oil of A. edulis plants collected in Dourados (EOAE-D) and Bonito (EOAE-B), two cities in Mato Grosso do Sul State, Brazil. Additionally, we evaluated the anti-inflammatory effects of the essential oil, as well as that of the major compounds (caryophyllene oxide and α-zingiberene), in experimental in vivo models of inflammation in mice. MATERIALS AND METHODS: Leaves were collected from plants at both sites in July 2018. The composition of the essential oil (EOAE-D and EOAE-B) was determined by GC/MS, and major compounds (caryophyllene oxide and α-zingiberene) were isolated and identified by chromatographic methods and NMR spectroscopy. Anti-inflammatory capacities were assessed using two classical models of inflammatory models, carrageenan- and CFA-induced paw inflammation (mechanical and thermal hyperalgesia). RESULTS: Both EOAE-D and EOAE-B showed sesquiterpenes as a major constituent, namely, caryophyllene oxide (29.5%) and α-zingiberene (45.0%), respectively. In tests, EOAE, caryophyllene oxide and α-zingiberene-induced antiedematogenic and antihyperalgesic effects were found in the different utilized models. CONCLUSIONS: The results indicate that samples from the two cities differed in chemical composition but not in their anti-inflammatory and antihyperalgesic effects. This finding corroborates the use of A. edulis as a medicinal plant and indicates its potential in the therapy of inflammatory conditions.

Bacillus subtilis-based probiotic promotes bone growth by inhibition of inflammation in broilers subjected to cyclic heating episodes.

Heat stress as an environmental stressor causes abnormal bone remodeling and microarchitectural deterioration. The objective of this study was to investigate the effects of a Bacillus subtilis-based probiotic on bone mass of broilers subjected to cycling high ambient temperature. One hundred and twenty 1-day-old Ross 708 male broiler chicks were randomly assigned to 2 dietary treatments (12 pens per treatment): control diet and the control diet plus 250-ppm probiotic consisting of 3 strains of Bacillus subtilis. Room temperature was gradually decreased from 35°C on day 1 by 0.5°C/d until day 15, when ambient temperature was increased from 28°C to 32°C for 10 h (07:00 h-17:00 h) daily until day 44. Samples of blood, leg bones (tibia and femur), and brains (raphe nuclei and hypothalamus) were collected at day 43, while latency to lie test was conducted at day 44. Compared with controls, probiotic supplementation increased bone mineral content, weight, size, weight to length index, and reduced robusticity index in the tibia and femur (P < 0.05) of broilers subjected to heat stress. Serum concentrations of c-terminal telopeptide of type I collagen (CTX) were reduced (P = 0.02) by the probiotic supplementation, while ionized calcium, phosphate, and osteocalcin were not affected (P > 0.05). Moreover, tumor necrosis factor-α (TNF-α) in probiotic fed broilers was decreased (P = 0.003) without changes of plasma interleukin (IL)-6, IL-10, interferon-γ, and corticosterone concentrations. There were no treatment effects on the concentrations of peripheral serotonin and central serotonin and catecholamines (norepinephrine, epinephrine, and dopamine) as well as their metabolites. These results may indicate that dietary supplementation of Bacillus subtilis-based probiotic increases bone growth in broilers under a cyclic heating episode probably via inhibition of bone resorption, resulting from downregulation of the circulating TNF-α and CTX. Dietary probiotic supplementation may be a management strategy for increasing skeletal health of broilers under hot weather.

Nutritional Targeting of the Microbiome as Potential Therapy for Malnutrition and Chronic Inflammation.

Homeostatic interactions with the microbiome are central for a healthy human physiology and nutrition is the main driving force shaping the microbiome. In the past decade, a wealth of preclinical studies mainly using gnotobiotic animal models demonstrated that malnutrition and chronic inflammation stress these homeostatic interactions and various microbial species and their metabolites or metabolic activities have been associated with disease. For example, the dysregulation of the bacterial metabolism of dietary tryptophan promotes an inflammatory environment and susceptibility to pathogenic infection. Clinical studies have now begun to evaluate the therapeutic potential of nutritional and probiotic interventions in malnutrition and chronic inflammation to ameliorate disease symptoms or even prevent pathogenesis. Here, we therefore summarize the recent progress in this field and propose to move further towards the nutritional targeting of the microbiome for malnutrition and chronic inflammation.