Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

Excess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes. The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this question, transgenic mice with enhanced DCs lifespan and immunogenicity (DChBcl-2 mice) are challenged with a high-fat diet. Those mice display resistance to DIO and metabolic alterations. The DIO-resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DChBcl-2 DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function which is associated with strong intestinal IgA, Th17 and T regulatory immune responses. Microbiota composition and function analyses reveal that the DChBcl-2 mice microbiota is characterized by lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to WT mice demonstrating that maintenance of DCs tolerogenic ability sustains a microbiota able to drive DIO resistance. DCs tolerogenic function is revealed as a new potent target in metabolic disease management.

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Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

10.1101/2020.10.22.350033 ◽

2020 ◽

Author(s):

Emelyne Lécuyer ◽

Tiphaine Le Roy ◽

Aurélie Gestin ◽

Amélie Lacombe ◽

Catherine Philippe ◽

...

Keyword(s):

Dendritic Cells ◽

Metabolic Diseases ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Low Grade ◽

Obesity And Diabetes ◽

Tolerogenic Dendritic Cells ◽

Tolerogenic Function ◽

And Function

ABSTRACTExcess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes.The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this question, transgenic mice with enhanced DCs lifespan and immunogenicity (DChBcl-2 mice), are challenged with a high fat diet.Those mice display resistance to DIO and metabolic alterations. The DIO resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DChBcl-2 DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function which is associated with strong intestinal IgA, Th17 and T regulatory immune responses.Microbiota composition and function analyses reveal that the DChBcl-2 mice microbiota is characterized by a lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to WT mice demonstrating that maintenance of DCs tolerogenic ability sustains a microbiota able to drive DIO resistance. DCs tolerogenic function is revealed as a new potent target in metabolic diseases management.

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Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

10.2337/figshare.14687523.v1 ◽

2021 ◽

Author(s):

Emelyne Lécuyer ◽

Tiphaine Le Roy ◽

Aurélie Gestin ◽

Amélie Lacombe ◽

Catherine Philippe ◽

...

Keyword(s):

Dendritic Cells ◽

Metabolic Diseases ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Low Grade ◽

Obesity And Diabetes ◽

Tolerogenic Dendritic Cells ◽

Tolerogenic Function ◽

And Function

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Butyrate as a Potential Preventive Therapy for Obesity

The Indian Journal of Nutrition and Dietetics ◽

10.21048/ijnd.2019.56.4.23688 ◽

2019 ◽

Vol 56 (4) ◽

pp. 439

Author(s):

P. Meena Kumari ◽

S. P. Muthukumar

Keyword(s):

Barrier Function ◽

Inflammatory Mediator ◽

Metabolic Diseases ◽

Current Knowledge ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Low Grade ◽

Metabolic Risk ◽

Metabolic Complications ◽

Anti Inflammatory

Due to its grave pathological role of obesity, comprehensive research is being continued to find out the causative factors involved in it. Recent advances in this field are increasingly recognized that there is a connection between diet, gut microbiota, intestinal barrier function and the low-grade inflammation that characterize the progression from obesity to metabolic disturbances, making dietary strategies to modulate the intestinal environment is important. In this context, the ability of some Gram-positive anaerobic bacteria to produce the shortchain fatty acid butyrate is impressive. A lower abundance of butyrate-producing bacteria has been associated with metabolic risk in humans. Recent studies suggest that butyrate might have been linked with metabolic risk in humans, and recommend that butyrate might have an anti-inflammatory mediator in metabolic diseases, and the potential of butyrate can alleviate obesity-related metabolic complications, possibly due to its ability to enhance the intestinal barrier function. Endogenous butyrate synthesis, delivery, and absorption by colonocytes have been well studied. Butyrate exerts its function by serving as a histone deacetylase (HDAC) inhibitor or signaling through several G Protein-Coupled Receptors (GPCRs). Latterly butyrate has gained selective attention for its favorable effects on intestinal homeostasis and energy metabolism. With anti-inflammatory properties, butyrate improves intestinal barrier function and mucosal immunity. Growing proof has highlighted the influence of butyrate on obesity. In this review the current knowledge on the features of butyrate, especially its potential effects and mechanisms involved in intestinal health and obesity. Here we review and discuss the potentials of butyrate as an anti-inflammatory mediator in obesity and the potential for dietary interventions increasing intestinal availability of butyrate.

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BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

Frontiers in Immunology ◽

10.3389/fimmu.2020.570920 ◽

2020 ◽

Vol 11 ◽

Author(s):

Runze Quan ◽

Chaoyue Chen ◽

Wei Yan ◽

Ying Zhang ◽

Xi Zhao ◽

...

Keyword(s):

Barrier Function ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Survival Rates ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Barrier Dysfunction ◽

Protein Levels ◽

Lps Challenge ◽

Endotoxemia Model

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

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Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

International Journal of Molecular Sciences ◽

10.3390/ijms22052602 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2602

Author(s):

Emilie Viennois ◽

Benoit Chassaing

Keyword(s):

Intestinal Inflammation ◽

Tumor Development ◽

Low Grade ◽

Gastrointestinal Cancers ◽

Cancer Initiation ◽

And Function ◽

The Impact ◽

Chronic Intestinal Inflammation ◽

Low Grade Inflammation ◽

Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

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Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

Nutrients ◽

10.3390/nu13030850 ◽

2021 ◽

Vol 13 (3) ◽

pp. 850

Author(s):

María Ángeles Martín ◽

Sonia Ramos

Keyword(s):

Immune System ◽

Fruits And Vegetables ◽

Metabolic Diseases ◽

Nuclear Factor Κb ◽

Low Grade ◽

Beneficial Effects ◽

Health And Disease ◽

Immunological Reactions ◽

And Function ◽

Positive Properties

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

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Intestinal Barrier Function and Performance of Broiler Chickens Fed Additional Arginine, Combination of Arginine and Glutamine or an Amino Acid-Based Solution

Animals ◽

10.3390/ani11082416 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2416

Author(s):

Reza Barekatain ◽

Tristan Chalvon-Demersay ◽

Clive McLaughlan ◽

William Lambert

Keyword(s):

Amino Acid ◽

Intestinal Permeability ◽

Broiler Chickens ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Basal Diet ◽

Intestinal Barrier Function ◽

Glutathione Synthetase ◽

Feed Conversion ◽

Experimental Treatments

Two experiments were conducted to investigate the effect of arginine (Arg); the combination of Arg and glutamine (Gln); as well as an amino acid-based solution (MIX) containing Arg, Gln, threonine (Thr), and grape extract, on performance, intestinal permeability, and expression of selected mechanistic genes. Using 240 male Ross 308 off-sex broiler chickens, four experimental treatments were replicated six times with 10 birds per replicate. The experimental treatments included 5 g/kg Arg, 2.5 g/kg Arg and 2.5 g/kg Gln, and 1 g/kg MIX added to a basal diet as control. In the second study, the four dietary treatments were then given to 24 birds with or without a synthetic glucocorticoid, dexamethasone (DEX), as a gut dysfunction model. Feed conversion ratio was improved by all the supplemented treatments from day 7 to 35 of age (p < 0.001). DEX injections increased (p < 0.001) the intestinal permeability in all treatments, which tended to be reversed by Arg or MIX. Additional Arg, Arg-Gln, and MIX suppressed (p < 0.05) the overexpression of IL-1β generated by DEX. Feeding birds with MIX treatment increased (p < 0.05) expression of SGLT-1 and glutathione synthetase. In conclusion, tested amino acid supplements were effective in improving feed efficiency and restraining intestinal inflammation caused by DEX through IL-1β pathway.

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Anthocyanins and intestinal barrier function: a review

Journal of Food Bioactives ◽

10.31665/jfb.2019.5175 ◽

2019 ◽

Vol 5 ◽

pp. 18-30 ◽

Cited By ~ 4

Author(s):

Jonathan C. Valdez ◽

Bradley W. Bolling

Keyword(s):

Barrier Function ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Barrier Dysfunction ◽

Intestinal Barrier Dysfunction ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Berry Anthocyanins ◽

Chronic Intestinal Inflammation

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.

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The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation

Nutrients ◽

10.3390/nu10080988 ◽

2018 ◽

Vol 10 (8) ◽

pp. 988 ◽

Cited By ~ 97

Author(s):

Kaisa Hiippala ◽

Hanne Jouhten ◽

Aki Ronkainen ◽

Anna Hartikainen ◽

Veera Kainulainen ◽

...

Keyword(s):

Barrier Function ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Intestinal Health ◽

Beneficial Effects ◽

Beneficial Action ◽

Anti Inflammatory ◽

Major Factors ◽

Extracellular Structures

The intestinal microbiota, composed of pro- and anti-inflammatory microbes, has an essential role in maintaining gut homeostasis and functionality. An overly hygienic lifestyle, consumption of processed and fiber-poor foods, or antibiotics are major factors modulating the microbiota and possibly leading to longstanding dysbiosis. Dysbiotic microbiota is characterized to have altered composition, reduced diversity and stability, as well as increased levels of lipopolysaccharide-containing, proinflammatory bacteria. Specific commensal species as novel probiotics, so-called next-generation probiotics, could restore the intestinal health by means of attenuating inflammation and strengthening the epithelial barrier. In this review we summarize the latest findings considering the beneficial effects of the promising commensals across all major intestinal phyla. These include the already well-known bifidobacteria, which use extracellular structures or secreted substances to promote intestinal health. Faecalibacterium prausnitzii, Roseburia intestinalis, and Eubacterium hallii metabolize dietary fibers as major short-chain fatty acid producers providing energy sources for enterocytes and achieving anti-inflammatory effects in the gut. Akkermansia muciniphila exerts beneficial action in metabolic diseases and fortifies the barrier function. The health-promoting effects of Bacteroides species are relatively recently discovered with the findings of excreted immunomodulatory molecules. These promising, unconventional probiotics could be a part of biotherapeutic strategies in the future.

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Desmethylbellidifolin Attenuates Dextran Sulfate Sodium-Induced Colitis: Impact on Intestinal Barrier, Intestinal Inflammation and Gut Microbiota

Planta Medica ◽

10.1055/a-1506-3476 ◽

2021 ◽

Author(s):

Jiaqi Wu ◽

Yuzheng Wu ◽

Yue Chen ◽

Mengyang Liu ◽

Haiyang Yu ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

Activity Index ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Function Evaluation ◽

Biological Drugs

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

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