Short chain fatty acid butyrate, a breast milk metabolite, enhances immature intestinal barrier function genes in response to inflammation in vitro and in vivo

Author(s):  
Yanan Gao ◽  
Brittany Davis ◽  
Weishu Zhu ◽  
Nan Zheng ◽  
Di Meng ◽  
...  

Infants born under 1500 grams have an increased incidence of necrotizing enterocolitis in the ileum and the colon which is a life-threatening intestinal necrosis. This is in part due to excessive inflammation in the immature intestine to colonizing bacteria because of an immature innate immune response. Breastmilk complex carbohydrates create metabolites of colonizing bacteria in the form of short-chain fatty acids (SCFAs). We studied the effect of breastmilk metabolites, SCFAs, on immature intestine with regard to anti-inflammatory effects. This showed that acetate, propionate and butyrate were all anti-inflammatory to an IL-1β inflammatory stimulus. In this study, to further define the mechanism of anti-inflammation, we created transcription profiles of RNA from immature human enterocytes after exposure to butyrate with and without an IL-1β inflammatory stimulus. We demonstrated that butyrate stimulates an increase in tight-junction and mucus genes and if we inhibit these genes the anti-inflammatory effect is partially lost. SCFAs, products of microbial metabolism of complex carbohydrates of breastmilk oligosaccharides, have been found with this study to induce an anti-IL-1β response that is associated with an upregulation of tight junctions and mucus genes in epithelial cells (H4 cells). These studies suggest that breastmilk in conjunction with probiotics can reduce excessive inflammation with metabolites that are anti-inflammatory and stimulate an increase in the mucosal barrier.

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO

2021 ◽  
Author(s):  
Bolaji Lilian Ilesanmi-Oyelere ◽  
Marlena Cathorina Kruger

Prebiotics, probiotics and synbiotics has been shown to enhance calcium absorption, gut and bone health. Probiotics are also known to ferment prebiotics to produce the fermentative substrates such as short chain fatty acids (SCFAs), mainly acetate, butyrate and propionate with the help of beneficial micro-organisms in the gut. The expression of these SCFAs has been associated with the inhibition of osteoclast differentiation and bone resorption both in vitro and in vivo. In this review, we discuss the benefits of SCFAs and ways in which prebiotics and probiotics affect bone health by the reduction of inflammation in the gut and the bone.


Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2776 ◽  
Author(s):  
Miranda Tsang ◽  
Sau-Wan Cheng ◽  
Jing Zhu ◽  
Karam Atli ◽  
Ben Chan ◽  
...  

Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative medicines possess a potential in the management of allergic asthma. Previous clinical, in vivo, and in vitro studies have shown that the Pentaherbs formula (PHF) comprising five traditional Chinese herbal medicines Lonicerae Flos, Menthae Herba, Phellodendri Cortex, Moutan Cortex, and Atractylodis Rhizoma possesses an anti-allergic and anti-inflammatory potential through suppressing various immune effector cells. In the present study, to further investigate the anti-inflammatory activities of PHF in allergic asthma, intragastrical administration of PHF was found to reduce airway hyperresponsiveness, airway wall remodeling and goblet cells hyperplasia in an ovalbumin (OVA)-induced allergic asthma mice model. PHF also significantly suppressed pulmonary eosinophilia and asthma-related cytokines IL-4 and IL-33 in bronchoalveolar lavage (BAL) fluid. In addition, PHF modulated the splenic regulatory T cells population, up-regulated regulatory interleukin (IL)-10 in serum, altered the microbial community structure and the short chain fatty acids content in the gut of the asthmatic mice. This study sheds light on the anti-inflammatory activities of PHF on allergic asthma. It also provides novel in vivo evidence that herbal medicines can ameliorate symptoms of allergic diseases may potentially prevent the development of subsequent atopic disorder such as allergic asthma through the influence of the gut microbiota.


2020 ◽  
Vol 8 (5) ◽  
pp. 788 ◽  
Author(s):  
Heejung Kim ◽  
Yunju Jeong ◽  
Sini Kang ◽  
Hyun Ju You ◽  
Geun Eog Ji

Faecalibacterium prausnitzii is a major commensal bacterium in the human gut. It produces short-chain fatty acids that promote intestinal health. However, the bacterium is extremely oxygen-sensitive, making it difficult to develop as a probiotic. To facilitate practical application of F. prausnitzii, we investigated factors that affect its growth and mammalian gut colonization. We evaluated cross-feeding interactions between F. prausnitzii and seven Bifidobacterium strains, and the anti-inflammatory properties of bacterial metabolites produced in co-culture, in vitro and in vivo. Co-culture of F. prausnitzii and Bifidobacterium catenulatum, with fructooligosaccharides as an energy source, resulted in the greatest viable cell-count and butyrate production increases. Further, the co-culture supernatant reduced the amount of proinflammatory cytokines produced by HT-29 cells and RAW 264.7 macrophages, an effect that was similar to that of butyrate. Furthermore, feeding mice both Faecalibacterium and Bifidobacterium enhanced F. prausnitzii gut colonization. Finally, feeding the co-culture supernatant decreased interleukin 8 levels in the colon and increased butyrate levels in the cecum in the dextran sodium sulfate-induced colitis mouse model. These observations indicate that the Faecalibacterium-Bifidobacterium co-culture exerts an anti-inflammatory effect by promoting F. prausnitzii survival and short-chain fatty acid production, with possible implications for the treatment of inflammatory bowel disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hee Seo ◽  
Hyunbin Seong ◽  
Ga Yun Kim ◽  
Yu Mi Jo ◽  
Seong Won Cheon ◽  
...  

The use of probiotic starters can improve the sensory and health-promoting properties of fermented foods. In this study, we developed an anti-inflammatory probiotic starter, Limosilactobacillus reuteri EFEL6901, for use in kimchi fermentation. The EFEL6901 strain was safe for use in foods and was stable under human gastrointestinal conditions. In in vitro experiments, EFEL6901 cells adhered well to colonic epithelial cells and decreased nitric oxide production in lipopolysaccharide-induced macrophages. In in vivo experiments, oral administration of EFEL6901 to DSS-induced colitis mice models significantly alleviated the observed colitis symptoms, prevented body weight loss, lowered the disease activity index score, and prevented colon length shortening. Analysis of these results indicated that EFEL6901 played a probiotic role by preventing the overproduction of pro-inflammatory cytokines, improving gut barrier function, and up-regulating the concentrations of short-chain fatty acids. In addition, EFEL6901 made a fast growth in a simulated kimchi juice and it synthesized similar amounts of metabolites in nabak-kimchi comparable to a commercial kimchi. This study demonstrates that EFEL6901 can be used as a suitable kimchi starter to promote gut health and product quality.


Author(s):  
Tindaro Bongiovanni ◽  
Marilyn Ong Li Yin ◽  
Liam Heaney

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.


1978 ◽  
Vol 40 (1) ◽  
pp. 125-131 ◽  
Author(s):  
J. D. Edwards-Webb ◽  
S. Y. Thompson

1. The lipolysis of cow's milk fat by salivary lipase (EC 3.1.1.3) in the preruminant calf has been studied in vitro by a simulated abomasal digestion, and also in vivo by examining the abomasal effluent collected over 12 h after giving whole milk to a calf.2. In the in vitro experiment the liquid drained from the clot contained a higher proportion of short-chain fatty acids than the abomasal effluent in the in vivo experiment. This was considered to indicate the absorption of short-chain free fatty acids from within the abomasum.3. Preferential release of short-chain fatty acids both in vitro and in vivo was observed.4. The outflow of butyric acid from the abomasum of the calf was initially rapid, but had levelled off at approximately 6 h, whereas the outflow of a typical long-chain fatty acid (palmitic) was fairly constant over the 12 h.Butyric acid predominated in the free fatty acids of abomasal effluent 0.5 h after feeding (668 mmol/mol total free fatty acids) but had become a minor component by 12 h (15 mmol/mol total free fatty acids).5. The mean amounts of free and esterified fatty acids (mmol/mol fatty acid ingested) present in the abomasal effluent from the 12 h collection period were: triglyceride 465, diglyceride 215, monoglyceride 68, free fatty acid 252. These values showed that only one-third of esterified fatty acids ingested are lipolysed to absorbable products by salivary lipase.


2020 ◽  
Vol 21 (2) ◽  
pp. 445 ◽  
Author(s):  
Sini Kang ◽  
Hyun Ju You ◽  
Yeong-Geun Lee ◽  
Yunju Jeong ◽  
Tony V. Johnston ◽  
...  

Short-chain fatty acids (SCFAs), especially butyrate, produced in mammalian intestinal tracts via fermentation of dietary fiber, are known biofunctional compounds in humans. However, the variability of fermentable fiber consumed on a daily basis and the diversity of gut microbiota within individuals often limits the production of short-chain fatty acids in the human gut. In this study, we attempted to enhance the butyrate levels in human fecal samples by utilizing butyl-fructooligosaccharides (B-FOS) as a novel prebiotic substance. Two major types of B-FOS (GF3-1B and GF3-2B), composed of short-chain fructooligosaccharides (FOS) bound to one or two butyric groups by ester bonds, were synthesized. Qualitative analysis of these B-FOS using Fourier transform infrared (FT-IR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), nuclear magnetic resonance (NMR) and low-resolution fast-atom bombardment mass spectra (LR-FAB-MS), showed that the chemical structure of GF3-1B and GF3-2B were [O-(1-buty-β-D-fru-(2→1)-O-β-D-fru-(2→1)-O-β-D-fru-O-α-D-glu] and [O-(1-buty)-β-D-fru-(2→1)-O-β-D-fru-(2→1)-O-(4-buty)-β-D-fru-O-α-D-glu], respectively. The ratio of these two compounds was approximately 5:3. To verify their biofunctionality as prebiotic oligosaccharides, proliferation and survival patterns of human fecal microbiota were examined in vitro via 16S rRNA metagenomics analysis compared to a positive FOS control and a negative control without a carbon source. B-FOS treatment showed different enrichment patterns on the fecal microbiota community during fermentation, and especially stimulated the growth of major butyrate producing bacterial consortia and modulated specific butyrate producing pathways with significantly enhanced butyrate levels. Furthermore, the relative abundance of Fusobacterium and ammonia production with related metabolic genes were greatly reduced with B-FOS and FOS treatment compared to the control group. These findings indicate that B-FOS differentially promotes butyrate production through the enhancement of butyrate-producing bacteria and their metabolic genes, and can be applied as a novel prebiotic compound in vivo.


2003 ◽  
Vol 90 (3) ◽  
pp. 625-634 ◽  
Author(s):  
M. Blümmel ◽  
A. Karsli ◽  
J. R. Russell

The efficiency of rumen microbial production (EMP)in vitroandin vivowas examined for three roughages (lucerne (Medicago sativaL.) hay, oat (Avenia sativaL.)–berseem clover (Trifolium alexandrinumcultivar BigBee) hay and maize (Zea maysL.) crop residue (MCR)) and for five isonitrogenous (106 g crude protein (N × 6·25)/kg) diets formulated from lucerne hay, oat–berseem clover hay, MCR, soya-bean meal and maize grain to provide degradable intake protein for the production of 130 g microbial protein/kg total digestible nutrients. EMPin vivowas determined by intestinal purine recovery in sheep and ranged from 240 to 360 g microbial biomass/kg organic matter truly degraded in MCR and in one of the diets respectively (P<0·05). EMPin vitrowas estimated by the substrate degraded: gas volume produced thereby (termed partitioning factor, PF (mg/ml)) at times of estimated peak microbial production and after 16·0 and 24·0h of incubation. For the diets, PF values were significantly related to EMPin vivoat peak microbial production (P= 0·04), but not after 16·0 (P= 0·08) and 24·0h (P= 0·66). For roughages, PF values were significantly related to EMPin vivoonly when measured after 16·0 h (P= 0·04). For MCR and diets, a close non-linear relationship was found between PF values at peak microbial production and EMPin vivo(R20·99,P<0·0001) suggesting a maximum EMPin vivoof 0·39. Low gas production per unit substrate degraded (high PF) was associated with high EMPin vivo.Thein vitrostudy of the products of fermentation, short-chain fatty acids, gases and microbial biomass (by purine analysis) after 16·0h of incubation showed very strong relationships (R2≥ 0·89,P<0·0001) between short-chain fatty acids, gases and gravimetrically measured apparent degradability. Except for maize grain, the true degradability of organic matter estimated by neutral-detergent solution treatment agreed with the sum of the products of fermentation (R20·81,P=0·0004). After 16·0h of incubation, the synergistic effects of diet ingredient on diets were greater for microbial biomass (18%) than for short-chain fatty acids and gas production (7 %). It is concluded that measurement of gas production only gives incomplete information about fodder quality; complementation of gas measurements by true degradability measurements is recommended.


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