scholarly journals Commensal bacteria act as a broad genetic buffer in Drosophila during chronic under-nutrition

2018 ◽  
Author(s):  
Dali Ma ◽  
Maroun Bou-Sleiman ◽  
Pauline Joncour ◽  
Claire-Emmanuelle Indelicato ◽  
Michael Frochaux ◽  
...  

SummaryEukaryotic genomes encode several well-studied buffering mechanisms that robustly maintain invariant phenotypic outcome despite fluctuating environmental conditions. Here we show that the gut microbiota, represented by a single Drosophila facultative symbiont, Lactobacillus plantarum (LpWJL), acts also as a broad genetic buffer that masks the contribution of the cryptic genetic variations in the host under nutritional stress. During chronic under-nutrition, LpWJL consistently reduces variation in different host phenotypic traits and ensures robust organ patterning; LpWJL also decreases genotype-dependent expression variation, particularly for development-associated genes. We further demonstrate that LpWJL buffers via reactive oxygen species (ROS) signaling whose inhibition severely impairs microbiota-mediated phenotypic robustness. We thus identified an unexpected contribution of facultative symbionts to Drosophila fitness by assuring developmental robustness and phenotypic homogeneity in times of nutritional stress.

2007 ◽  
Vol 26 (21) ◽  
pp. 4457-4466 ◽  
Author(s):  
Amrita Kumar ◽  
Huixia Wu ◽  
Lauren S Collier-Hyams ◽  
Jason M Hansen ◽  
Tengguo Li ◽  
...  

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Maria F Ribeiro ◽  
André A Santos ◽  
Marta B Afonso ◽  
Pedro M Rodrigues ◽  
Sónia Sá Santos ◽  
...  

Abstract The influence of dietary factors on brain health and mental function is becoming increasingly recognized. Similarly, mounting evidence supports a role for gut microbiota in modulating central nervous system function and behaviour. Still, the molecular mechanisms responsible for the impact of diet and associated microbiome in adult neurodegeneration are still largely unclear. In this study, we aimed to investigate whether and how changes in diet-associated microbiome and its metabolites impact on adult neurogenesis. Mice were fed a high-fat, choline-deficient diet, developing obesity and several features of the metabolic syndrome, including non-alcoholic steatohepatitis. Strikingly, our results showed, for the first time, that animals fed with this specific diet display premature increased neurogenesis, possibly exhausting the available neural stem cell pool for long-term neurogenesis processes. The high-fat, choline-deficient diet further induced neuroinflammation, oxidative stress, synaptic loss and cell death in different regions of the brain. Notably, this diet-favoured gut dysbiosis in the small intestine and cecum, up-regulating metabolic pathways of short-chain fatty acids, such as propionate and butyrate and significantly increasing propionate levels in the liver. By dissecting the effect of these two specific short-chain fatty acids in vitro, we were able to show that propionate and butyrate enhance mitochondrial biogenesis and promote early neurogenic differentiation of neural stem cells through reactive oxygen species- and extracellular signal-regulated kinases 1/2-dependent mechanism. More importantly, neurogenic niches of high-fat, choline-deficient-fed mice showed increased expression of mitochondrial biogenesis markers, and decreased mitochondrial reactive oxygen species scavengers, corroborating the involvement of this mitochondrial stress-dependent pathway in mediating changes of adult neurogenesis by diet. Altogether, our results highlight a mitochondria-dependent pathway as a novel mediator of the gut microbiota–brain axis upon dietary influences.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Fernanda Priviero ◽  
Vanessa Dela Justina ◽  
Olufunke O Arishe ◽  
R Clinton Webb

Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite related with cardiovascular diseases. Circulating levels of TMAO are increased in diabetes and TMAO is associated with the development of insulin resistance. We aimed to investigate if TMAO impairs vascular reactivity in diabetes. The aorta of 16-week old male diabetic (db/db) and db/+ mice were mounted in a myograph and concentration-response curves to acetylcholine (ACh; 1 nM - 10 μM), sodium nitroprusside (SNP; 0.1 nM - 1 μM) and phenylephrine (PE; 1 nM - 10 μM) were obtained in the presence of TMAO (100 mM, 30 min), repeated in the presence of the antioxidant tempol (10 μM), the NLRP3 inhibitor (MCC950, 1 μM) or IL-1β receptor antagonist (IL1RA, 20 ng/mL). TMAO did not affect the contraction of PE or relaxation to SNP in aorta of db/db or db/+ mice, but decreased the potency of ACh in the aorta of db/+ (pEC 50 : 7.96 + 0.22 vs 7.25 + 0.16, lean or TMAO, respectively) and db/db (pEC 50 : 7.91 + 0.10 vs 7.17 + 0.09, db/db vs TMAO, respectively). In db/+ mice, tempol improved the potency of ACh (pEC 50 - TMAO: 7.05 + 0.21 vs TMAO + tempol 7.42 + 0.15) while further impairment in the relaxation to ACh was seen in the presence of MCC950 or IL1RA. In conclusion, TMAO impairs endothelium-dependent relaxation of aorta through the production of reactive oxygen species.


Author(s):  
Rahul S. Patil ◽  
Ashwini D. Jagdale ◽  
Megha L. Nalawade ◽  
Laxman N. Bavkar ◽  
Akalpita U. Arvindekar

Objective: To evaluate the use of protein glycation inhibitors and probiotics to ameliorate secondary complications in diabetes and to improve gut microbiota respectively in high fructose fed Wistar rat.Methods: The study was conducted on male Wistar rats for 7 d. Blood glucose levels in oral glucose tolerance test (OGTT) were measured using glucometer, serum parameters were analyzed using commercial kits, antioxidant status was evaluated by measuring superoxide dismutase (SOD) and catalase (CAT) levels, total reactive oxygen species were estimated using a fluorescent 2’, 7’-dichlorofluorescin diacetate (DCF-DA) dye, and tissue fluorescence of liver, kidney and intestine were measured using a spectrofluorimeter.Results: OGTT pattern shows significant increase in blood glucose of fructose fed rats i.e. 154 mg/dl while, in aminoguanidine (AMG) treated and gut microbiota modulated animals it is 137 and 119 mg/dl resp. after 30 min on glucose administration. Marked reduction was found in SOD 6.37 and 11.25 mg/dl and catalase 186 and 65.5 mg/dl in liver and kidney of fructose fed animals when compared to fructose+AMG and fructose+EUGI. There is 5-6 fold significant increase in general and specific tissue fluorescence of liver and kidney, and 2.2 fold increase in liver reactive oxygen species was observed in fructose fed group as compare to control animals. Significantly higher glycation was found in intestine of fructose fed animals (general fluorescence 2.1 and specific fluorescence 3.1 AU/mg), more than that of diabetic control rats (general fluorescence 0.9 and specific fluorescence 1.6 AU/mg), represented an evidence for adverse impact of excess fructose on healthy gut.Conclusion: The use of protein glycation inhibitor and use of pre and probiotics significantly improved the serum parameters and would prevent progression to secondary complications.


mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Boshuai Liu ◽  
Xiaoyan Zhu ◽  
Yalei Cui ◽  
Wenjing Wang ◽  
Hua Liu ◽  
...  

ABSTRACT In pregnant and lactating sows, metabolism and immunity undergo drastic changes, which can lead to constipation, abortion, and intrauterine growth restriction (IUGR) and reduce production performance. Dietary fiber can regulate animal gut microbiota, alleviate inflammatory responses, and improve performance. Here, 48 sows (Large × Landrace) were randomly allocated to groups including, control, and with alfalfa meal (AM), beet pulp, and soybean skin dietary supplementation for 60 days of gestation. The AM diet decreased IUGR, increased food intake during lactation, and promoted the reproductive performance and physical condition of sows. Further, the AM diet significantly reduced markers of intestinal permeability (reactive oxygen species and endotoxin) in sow serum, and of systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha) in sow feces and serum, as well as piglet serum, while it increased the anti-inflammatory marker, IL-10, in sow serum and feces. The AM diet also significantly affected gut microbiota by increasing the relative abundance of proinflammatory bacteria, while decreasing anti-inflammatory bacteria. Moreover, the total short-chain fatty acid (SCFA) content was higher in feces from sows fed an AM diet, with butyric acid content significantly higher during lactation, than in controls. Sow performance was correlated with intestinal permeability, inflammation, and gut microbiota, which were also vertically transmitted to piglets. Our results are significant for guiding feed management in the pig breeding industry. Further, the “sows to piglets” model provides a reference for the effect of dietary fiber on the gastrointestinal function of human mothers and infants. IMPORTANCE Although the direct effects of dietary fiber on gut microbiota composition have been studied extensively, systematic evaluation of different fiber sources on gut health and inflammatory responses of sows and their offspring has rarely been conducted. Excessive reactive oxygen species produced by overactive metabolic processes during late pregnancy and lactation of sows leads to increased endotoxin levels, disordered gut microbiota, decreased SCFA production, and secretion of proinflammatory factors, which in turn causes local inflammation of the gut, potential damage of the gut microbial barrier, increased gut permeability, increased blood endotoxin levels (resulting in systemic inflammation), and ultimately decreased sow and piglet performance. Our results showed that supplementation of the diet with alfalfa meal in mid and late pregnancy can reverse this process. Our findings lay a foundation for improving the gut health of sows and piglets and provide insights into the study of the gastrointestinal tract function in human mothers and infants.


2009 ◽  
pp. c3 ◽  
Author(s):  
Helena M. Cochemé ◽  
Michael P. Murphy

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.


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