scholarly journals Lung Immune Tone via Gut-Lung Axis: Gut-derived LPS and Short-chain Fatty Acids' immunometabolic regulation of Lung IL-1β, FFAR2 and FFAR3 Expression

2021 ◽  
Author(s):  
Qing Liu ◽  
Xiaoli Tian ◽  
Daisuke Maruyama ◽  
Mehrdad Arjomandi ◽  
Arun Prakash
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Lung Tissue ◽  
Gut Microbiome ◽  
Human Lung ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Human Lung Tissue ◽  
Chain Fatty Acids

Microbial metabolites produced by the gut microbiome, e.g. short-chain fatty acids (SCFA), have been found to influence lung physiology and injury responses. However, how lung immune activity is regulated by SCFA is unknown. We examined fresh human lung tissue and observed the presence of SCFA with inter-individual variability. In vitro, SCFA were capable of modifying the metabolic programming in LPS-exposed alveolar macrophages (AM). We hypothesized that lung immune tone could be defined by baseline detection of lung intracellular IL-1β. Therefore, we interrogated naïve mouse lungs with intact gut microbiota for IL-1β mRNA expression and localized its presence within alveolar spaces, specifically within AM subsets. We established that metabolically active gut microbiota, that produce SCFA, can transmit LPS and SCFA to the lung and thereby could create primed lung immunometabolic tone. To understand how murine lung cells sensed and upregulated IL-1β in response to gut microbiome-derived factors, we determined that, in vitro, AM and AT2 cells expressed SCFA receptors, FFAR2, FFAR3, and IL-1β but with distinct expression patterns and different responses to LPS. Finally, we observed that IL-1β, FFAR2 and FFAR3 were expressed in isolated human AM and AT2 cells ex-vivo, but in fresh human lung sections in situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells point to an important role for the gut microbiome and their SCFA in establishing and regulating lung immune tone.

Abstract P485: Association of Hypertension With the Gut Microbiome and Serum Short-chain Fatty Acids

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Moira K Differding ◽  
Lawrence J Appel ◽  
Nisa Maruthur ◽  
Stephen Juraschek ◽  
Edgar R Miller ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Self Report ◽  
Short Chain ◽  
Inverse Association ◽  
Negatively Associated ◽  
Adult Cancer Survivors ◽  
Chain Fatty Acids

Background: Murine models indicate that gut microbiota, and the short chain fatty acids (SCFAs) they produce from fermentation of fiber, play a role in blood pressure (BP) regulation. However, few human studies have examined how gut microbiota and serum SCFAs are associated with hypertension. Objective: We examined associations of gut microbiota composition and serum SCFAs with hypertension and BP, hypothesizing an inverse association with serum SCFAs. Methods: We performed a cross-sectional analysis of baseline data from a trial of overweight and obese adult cancer survivors. We measured 1 ) the gut microbiome by extracting microbial DNA from stool and sequencing the 16S rRNA V4 region and 2 ) serum SCFA using liquid chromatography mass spectrometry. Hypertension was defined as systolic BP ≥ 130, diastolic BP ≥ 80 mmHg, self-report, or use of hypertension medications. We used beta-binomial models to test differential abundance of microbial amplicon sequence variants by hypertension , and linear regression to examine log-transformed SCFAs with BP. We adjusted models for age, sex, race, fiber, BMI and medications (in BP models). Results: Of 111 participants with complete data, 73 had hypertension. Hypertensive participants differed by age (mean 62 vs. 56y) and sex (73% vs. 90% female), but not race (46% black) or BMI (mean 35 kg/m 2 ). Alpha and beta diversity were not associated with hypertension (Ps>0.05). Hypertensive participants had higher abundance of Bacteroides, Parabacteroides, Bifidobacterium and Escherichia , and lower Lachnospiraceae, Haemophilus and Faecalibacterium ( Figure) . Serum acetate was negatively associated with systolic BP (β=-3.3 mmHg difference per 1 SD increment acetate, 95% CI: -6.1, -0.6); other SCFAs were not associated (Ps>0.05). Conclusion: A Bacteroides dominated microbiota was positively associated with hypertension. Acetate, the most abundant circulating SCFA, was negatively associated with BP. Determining whether the associations are causal or not warrants further investigation.

scholarly journals Muscadine Grape Extract Reduces Lung and Liver Metastasis in Mice with Triple Negative Breast Cancer in Association with Changes in the Gut Microbiome (P05-017-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh Austin ◽  
Ann Tallant ◽  
Patricia Gallagher
Keyword(s):  
Breast Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Triple Negative Breast Cancer ◽  
Gut Microbiome ◽  
Triple Negative ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Muscadine Grape ◽  
Chain Fatty Acids

Abstract Objectives The goal of this study was to determine if a proprietary muscadine grape seed and skin extract (MGE) inhibits triple negative breast cancer (TNBC) metastasis and alters the gut microbiota. Methods 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control group (n = 8) or a treatment group that received 0.1 mg/mL total phenolics MGE (Piedmont R&D) in the drinking water (n = 8). Mice were sacrificed after 4 weeks; tissues and fecal samples were collected for analysis. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases using the inForm© 2.2 software. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids were detected by gas chromatography (Microbiome Insights). Data are expressed as means ± SEM using student's t-test. Results MGE reduced Ki67 cell positivity in the lungs and livers of mice, indicating reduced metastatic proliferation (9.3 ± 0.9% vs 6.2 ± 0.7% and 5.0 ± 1.5% vs 0.77 ± 0.2% cells, respectively; P < 0.01), and decreased cancer associated fibroblasts in the lungs (5.3 ± 1.0% vs 3.0 ± 0.5% cells; P < 0.05), which are associated with metastasis. MGE significantly reduced the number (4.7 ± 0.7 vs 2.2 ± 0.4 tumors/field; P < 0.01) and size (1358 ± 48 vs 1121 ± 47 pixels; P < 0.01) of liver metastases, resulting in decreased metastatic tumor burden (6656 ± 1220 vs 3096 ± 644 total area in pixels; P < 0.01). Attenuated TNBC metastasis correlated with MGE-induced changes in gut microbiota. Alpha diversity (4.15 ± 0.10 vs 4.51 ± 0.13 Shannon index; P < 0.05) and the Firmicutes to Bacteroidetes ratio (0.37 ± 0.07 vs 0.76 ± 0.12; P < 0.05) were significantly increased in MGE-treated mice, indicating enhanced microbial richness and increased energy harvest by the gut microbiome. Butyrate-producing bacteria, such as Ruminococcus, Butyricicoccus and Lachnospiraceae, were increased with MGE (P < 0.05) as well as the anti-inflammatory compound butyrate relative to other short-chain fatty acids (25.0 ± 2.7% vs 75.3 ± 15.5%; P < 0.01). Conclusions These data show that MGE attenuates TNBC metastasis in association with alterations in the gut microbiome, suggesting that MGE may be an effective treatment against TNBC metastatic progression. Funding Sources Chronic Disease Research Fund.

The Athlete and Gut Microbiome: Short-chain Fatty Acids as Potential Ergogenic Aids for Exercise and Training

2021 ◽  
Author(s):  
Tindaro Bongiovanni ◽  
Marilyn Ong Li Yin ◽  
Liam Heaney
Keyword(s):  
Fatty Acids ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Future Research ◽  
Immune Functions ◽  
Additional Energy ◽  
Chain Fatty Acids

AbstractShort-chain fatty acids (SCFAs) are metabolites produced in the gut via microbial fermentation of dietary fibers referred to as microbiota-accessible carbohydrates (MACs). Acetate, propionate, and butyrate have been observed to regulate host dietary nutrient metabolism, energy balance, and local and systemic immune functions. In vitro and in vivo experiments have shown links between the presence of bacteria-derived SCFAs and host health through the blunting of inflammatory processes, as well as purported protection from the development of illness associated with respiratory infections. This bank of evidence suggests that SCFAs could be beneficial to enhance the athlete’s immunity, as well as act to improve exercise recovery via anti-inflammatory activity and to provide additional energy substrates for exercise performance. However, the mechanistic basis and applied evidence for these relationships in humans have yet to be fully established. In this narrative review, we explore the existing knowledge of SCFA synthesis and the functional importance of the gut microbiome composition to induce SCFA production. Further, changes in gut microbiota associated with exercise and various dietary MACs are described. Finally, we provide suggestions for future research and practical applications, including how these metabolites could be manipulated through dietary fiber intake to optimize immunity and energy metabolism.

scholarly journals Evolution of Intestinal Gases and Fecal Short-Chain Fatty Acids Produced in vitro by Preterm Infant Gut Microbiota During the First 4 Weeks of Life

2021 ◽  
Vol 9 ◽  
Author(s):  
Xuefang Wang ◽  
Juan Li ◽  
Na Li ◽  
Kunyu Guan ◽  
Di Yin ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Acetic Acid ◽  
Gut Microbiota ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Delivery Mode ◽  
Chain Fatty Acids

Background: The production of intestinal gases and fecal short-chain fatty acids (SCFAs) by infant gut microbiota may have a significant impact on their health, but information about the composition and volume of intestinal gases and SCFA profiles in preterm infants is scarce.Objective: This study examined the change of the composition and volume of intestinal gases and SCFA profiles produced by preterm infant gut microbiota in vitro during the first 4 weeks of life.Methods: Fecal samples were obtained at five time points (within 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks) from 19 preterm infants hospitalized in the neonatal intensive care unit (NICU) of Shanghai Children's Hospital, Shanghai Jiao Tong University between May and July 2020. These samples were initially inoculated into four different media containing lactose (LAT), fructooligosaccharide (FOS), 2′-fucosyllactose (FL-2), and galactooligosaccharide (GOS) and thereafter fermented for 24 h under conditions mimicking those of the large intestine at 37.8°C under anaerobic conditions. The volume of total intestinal gases and the concentrations of individual carbon dioxide (CO2), hydrogen (H2), methane (CH4), and hydrogen sulfide (H2S) were measured by a gas analyzer. The concentrations of total SCFAs, individual acetic acid, propanoic acid, butyric acid, isobutyric acid, pentanoic acid, and valeric acid were measured by gas chromatography (GC).Results: The total volume of intestinal gases (ranging from 0.01 to 1.64 ml in medium with LAT; 0–1.42 ml with GOS; 0–0.91 ml with FOS; and 0–0.44 ml with FL-2) and the concentrations of CO2, H2, H2S, and all six fecal SCFAs increased with age (p-trends &lt; 0.05). Among them, CO2 was usually the predominant intestinal gas, and acetic acid was usually the predominant SCFA. When stratified by birth weight (&lt;1,500 and ≥1,500 g), gender, and delivery mode, the concentration of CO2 was more pronounced among infants whose weight was ≥1,500 g than among those whose weight was &lt;1,500 g (p-trends &lt; 0.05).Conclusions: Our findings suggested that the intestinal gases and SCFAs produced by preterm infant gut microbiota in vitro increased with age during the first 4 weeks of life.

scholarly journals Effect of nutritionally complete formula on gut microbiota and their metabolite in fecal batch fermentation system

2021 ◽  
Vol 11 (12) ◽  
pp. 641
Author(s):  
Santad Wichienchot ◽  
Kridsada Keawyok
Keyword(s):  
Fatty Acids ◽  
Lactic Acid ◽  
Gut Microbiota ◽  
High Performance ◽  
Lactic Acid Production ◽  
Short Chain Fatty Acids ◽  
Uremic Toxins ◽  
Short Chain ◽  
Chain Fatty Acids

Background: Emerging evidence has revealed that the gut microbiota is significantly altered, contributing to the occurrence and development of chronic kidney disease (CKD). Therefore, the target of increasing short-chain fatty acids (SCFAs) and lactic acid production and reduction of uremic toxins were interested.   Objective: To study the effect of the nutritionally complete formula (Synplus) developed for hemodialysis patients on gut microbiota and their metabolite in in vitro fecal fermentation of healthy volunteers.Methods:  Fecal fermentation (in vitro) using batch culture in an environment mimicking human large intestine was used to study the change of gut microbiota by next generation sequencing (NGS) during fermentation of the developed formula (Synplus), commercial formula (Nepro®) and control. The gut metabolites were determined including short-chain fatty acids (acetic, propionic, and butyric) and lactic acid. The uremic toxins (p-cresol and indole) were determined by high performance liquid chromatography (HPLC).Results: The increase of Lactobacillus spp. (53.74%) and Bifidobacterium spp. (29.35%) was observed in the developed product (Synplus) compared with control at 48 hrs fermentation meanwhile, these genera were decreased in a commercial product (Nepro®). Moreover, the abundance of the genus Escherichia spp. (12.33%) was observed in Nepro® fermentation, with Escherichia albertii species which is a newly discovered pathogen of the gastrointestinal tract. Microbial metabolites produced by fecal fermentation of Synplus revealed that propionate, acetate, and butyrate increased significantly (p<0.05). All the samples evaluated exhibited acetate in abundance when compared to other SCFAs. Acetate was the most abundant SCFA in all samples. The concentrations of acetate for Synplus fermentation were 15.63±3.26, 147.29±2.39, 162.28±4.13 and 189.39±0.17 mM at 0, 12, 24, and 48 hrs respectively. Total SCFAs produced from Synplus was significantly increased (p<0.05) and higher than control and Nepro®, respectively. The concentration of p-cresol at 48 hrs fermentation for control, Synplus and Nepro® were 3.79±0.12, 6.31±2.37 and 11.59±0.10 µg/mL, respectively. The indole concentration of control, Synplus and Nepro® were 3.64±0.08, 15.06±3.56 and 12.81±1.68 µg/mL, respectively. There were also indicated that imbalance of gut microbiota was related with the ratio of uremic toxins (indole and p-cresol) to SCFAs.CONCLUSION: The synbiotic product containing prebiotic and probiotic may be used to improve gut microbiota thus reducing the risk of kidney disease.Keywords: synbiotic, gut microbiota, uremic toxins, SCFA, CKD

scholarly journals Lung Immune Tone Regulation by the Gut-Lung Immune Axis: Short-chain Fatty Acid Receptors FFAR2 and FFAR3, and IL-1β Expression Profiling in Mouse and Human Lung

2020 ◽  
Author(s):  
Qing Liu ◽  
Xiaoli Tian ◽  
Daisuke Maruyama ◽  
Mehrdad Arjomandi ◽  
Arun Prakash
Keyword(s):  
Lung Tissue ◽  
Gut Microbiome ◽  
Human Lung ◽  
Expression Patterns ◽  
Metabolic Programming ◽  
Short Chain ◽  
Alveolar Type ◽  
Human Lung Tissue

ABSTRACTMicrobial metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFA), can influence both local intestinal and distant lung physiology and response to injury. However, how lung immune activity is regulated by SCFAs is unknown. We examined fresh human lung tissue and observed the presence of SCFAs with large inter-individual and even intra-lobe variability. In vitro, SCFAs were capable of modifying the metabolic programming in both resting and LPS-exposed alveolar macrophages (AM). Additionally, since we hypothesized that lung immune tone could be defined through priming of the inflammasome (aka signal 1), we interrogated naïve mouse lungs for pro-IL-1β message and localized its presence within the alveolar space in situ, specifically in AM subsets, and in close proximity to alveolar type 2 epithelial (AT2) cells. We established that metabolically active gut microbiota, that produce SCFAs, can transmit LPS and SCFAs to the lung (potential sources of signal 1), and thereby could regulate lung immune tone and metabolic programming. To understand how murine lung cells sensed and upregulated IL-1β in response to gut-microbiome factors, we determined that in vitro, AM and AT2 cells expressed SCFA receptors, FFAR2, FFAR3, and IL-1β but with different expression patterns and LPS-inducibility. Finally, we observed that IL-1β, FFAR2 and FFAR3 were expressed both in isolated human AM and AT2 cells ex-vivo, but in fresh human lung sections in situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells supports an important role for the gut microbiome and SCFAs in regulating lung immune tone.

Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO
Keyword(s):  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

The Consumption of Galactomannan Effervescent Drinks made from Coconut Pulp Waste and Colonic Microbiota in Wistar Rats

2020 ◽  
Vol 15 (1) ◽  
pp. 52-56
Author(s):  
Sri Winarti ◽  
Agung Pasetyo
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Wistar Rats ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
E Coli ◽  
Colonic Microbiota ◽  
Male Wistar Rats ◽  
Lactobacillus Spp ◽  
Chain Fatty Acids

The consumption of prebiotics is known to affect the balance of gut microbiota. The purpose of this study was to explore how a galactomannan-rich effervescent drink can affect the population of Lactobacillus, Bifidobacterium, E. coli, and the concentration of short-chain fatty acids in the cecum of rats. Twenty-eight male Wistar rats (aged 2 months) were divided equally into 7 groups and treated orally each day for 15 days with 2 mL effervescent drinks with increasing levels of prebiotic galactomannan. The dosage of 500 mg galactomannan increased the growth of Lactobacillus spp. and Bifidobacterium spp. with inhibition of the growth of E.coli with increased formation of short-chain fatty acids such as acetate, propionate, and butyrate in the cecum of rats.

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