Nutritional Modulation of the Microbiome and Immune Response.
15 Sep 2020-Journal of Immunology (The American Association of Immunologists)-Vol. 205, Iss: 6, pp 1479-1487
TL;DR: Developing a deeper understanding of the relationship between diet, microbiota, and the immune system is of huge importance, given its impact on inflammatory diseases and its potential as an easily modifiable mediator of immunomodulation.
Abstract: The evolution of the immune system, diet, and the microbiome are interconnected. Dietary metabolites modulate the cells of the immune system both directly and indirectly via shifts in the composition of the intestinal microbiota and its products. As a result, overconsumption and malnutrition can have substantial effects on immune responses and inflammation. In resource-rich nations, diets high in processed foods, fat, and sugar can contribute to chronic inflammatory conditions, which are on the rise worldwide. Conversely, in resource-poor countries, malnutrition associated with food insecurity can lead to immunodeficiencies and shifts in the microbiome that drive intestinal inflammation. Developing a deeper understanding of the relationship between diet, microbiota, and the immune system is of huge importance, given its impact on inflammatory diseases and its potential as an easily modifiable mediator of immunomodulation.
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TL;DR: In this article, the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.
Abstract: The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an “inflammatory disorder”, with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system–microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.
123 citations
TL;DR: The evidence that the gut and lung microbiota are key players in the maintenance of healthy lungs, and as such, are potential targets for nutrition-based preventive strategies against lung disease in elderly populations is explored.
53 citations
Cites background from "Nutritional Modulation of the Micro..."
...It has been extensively reviewed in recent years (Barber et al., 2020; Burr et al., 2020; Dogra et al., 2020; Fassarella et al., 2020; Kolodziejczyk et al., 2019; Vandeputte and Joossens, 2020)....
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TL;DR: In this article , recent evidence and emerging concepts supporting the idea that our newfound relationship with nutrition in industrialized countries has fundamentally altered the way in which our immune system is wired are examined through the lens of studies showing that mild or transient reductions in dietary intake can enhance protective immunity while also limiting aberrant inflammatory responses.
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TL;DR: In this paper, the authors developed a microbiota-and diet-dependent mouse EED model and found that deletion of RORγT from Treg cells restored small intestinal vaccine-specific CD4 T-cell responses and vaccine-mediated protection upon challenge.
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References
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TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Abstract: The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
10,126 citations
"Nutritional Modulation of the Micro..." refers background in this paper
...to germ-free mice results in obesity in the recipient mice, whereas antibiotic treatment of obese mice reduces adipose inflammation and adiposity (21, 39, 40)....
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TL;DR: Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults.
Abstract: Importance More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010. Objective To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults. Design, Setting, and Participants Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey. Main Outcomes and Measures In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). Results In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children ( P = .03) and women ( P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006). Conclusions and Relevance Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.
7,532 citations
"Nutritional Modulation of the Micro..." refers background in this paper
...Overnutrition has led to the staggering rise in global obesity rates, which have nearly tripled over the last 40 years (9, 10)....
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TL;DR: It is found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice, demonstrating that changes in gut microbiota controls metabolic endotoxinemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability.
Abstract: OBJECTIVE— Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. RESEARCH DESIGN AND METHODS— We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. RESULTS— We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat–fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14 − / − mutant mice mimicked the metabolic and inflammatory effects of antibiotics. CONCLUSIONS— This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.
3,914 citations
"Nutritional Modulation of the Micro..." refers background in this paper
...bacterial products also likely lead to the potent induction of inflammatory cytokines (21, 33)....
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...to germ-free mice results in obesity in the recipient mice, whereas antibiotic treatment of obese mice reduces adipose inflammation and adiposity (21, 39, 40)....
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...Feeding mice HFD for 1 wk reduces the expression and alters the distribution of tight junction proteins, which is associated with increased intestinal permeability and bacterial product translocation (20, 21)....
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TL;DR: This study determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice, revealing that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
Abstract: Regulatory T cells (T regs ) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate T reg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic T regs . We determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic T reg pool and protect against colitis in a Ffar2 -dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
3,733 citations
TL;DR: It is shown that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice and ameliorated the development of colitis induced by adoptive transfer of CD4+ CD45RBhi T cells in Rag1−/− mice.
Abstract: Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
3,596 citations