ReviewIntestinal microflora and metabolic diseasesFlore intestinale et maladies métaboliques
Introduction
Our human microflora are an inherited feature resulting from our evolution. With the celebration of 200 years since the birth of Charles Darwin, it makes sense to consider that the development of human physiology could be the consequence of environmental factors such as microflora, which might even be thought of as a selection factor among humans. Indeed, the selection of the species comprising our microflora today could be considered to be the result of evolution, with some strains selected on the basis of our evolving genome. This means that the host–microflora relationship could be the result of a bidirectional selection process that has now established a shared ecology among the different members of the microflora and the host.
However, the molecular bases of this ecology and its interaction with the host need deciphering if we are to have access to the potentially vast new spectrum of strategies for the management of human physiology and treatment of diseases. Cancer and the inflammatory and metabolic diseases are among the first in line for the use of microflora-based therapeutic strategies.
Given the wide diversity of our entire body's microflora, this review focuses on the intestinal microflora, and its relationship with metabolic diseases and other related disorders. The choice of this narrow field of discussion is driven by the intuitive concept that feeding our body is also feeding our intestinal flora. Consequently, both the genome and metagenome contribute to the subtle balance of mechanisms involved in metabolism. We discuss here some of the most recent findings on the molecular mechanisms through which the intestinal microflora influence metabolic diseases.
Section snippets
Intestinal microflora: a mutual ecology
The intestine is inhabited by trillions of microorganisms, including bacteria, fungi and the Archaea. Two sets of microorganisms have been described. In one, the tasks performed by some members are partially known and are most likely beneficial to the host. However, the vast majority of species are neither beneficial nor harmful to human physiology, and their function remains completely unknown. These species are termed “normal flora”, or “microbiota”. It is estimated that 500 to 1000 different
Intestinal microflora and inflammatory diseases
The role of the intestinal microflora has been largely described in inflammatory diseases such as IBD, CD and UC. Although beyond the scope of this review, some concepts are helpful for understanding the origin of metabolic disorders. Indeed, it is now thought that obesity and diabetes are associated with a poor inflammatory status, leading to impaired insulin action and adipose tissue plasticity (Fig. 2, Fig. 3) [33], [34]. This means that the origin of metabolic inflammation could have some
Intestinal microflora and T1D
T1D is a T-cell-mediated autoimmune disease that results in destruction of the insulin-producing beta cells of the pancreas. T1D is known as “childhood”, “juvenile” or “insulin-dependent” diabetes, although it is not exclusively seen in childhood, as demonstrated by its growing incidence in adults. So far, there are no preventative measures against T1D, and the initiating cause of the immune-system damage is still not fully understood, although diet and exercise can help. However, a provocative
Intestinal microflora, obesity and type 2 diabetes (T2D)
In the USA, roughly one million diabetic patients are newly diagnosed each year. Given this growing number of cases, as well as the numbers of undiagnosed cases (one-third of patients are not aware of their disease), the treatment of diabetes remains a major therapeutic challenge that the entire population needs to address. Obesity has now been classified as the newest epidemic, as its occurrence is on the increase in Western countries. The World Health Organization (WHO) has estimated that 600
Intestinal microflora and increased metabolic endotoxaemia
A raised hepatic low-density lipoprotein (LDL)–high-density lipoprotein (HDL) ratio defines dyslipidaemia, an important feature of metabolic diseases. The LPS, the principal component of the outer membrane of Gram-negative bacteria and the most powerful of the proinflammatory molecules, is also a component of lipoprotein particles [62], [63]. The latter have been proposed to buffer LPS in response to septic shock [63], and to prevent an overt inflammatory response and fatality. As for the
Antibiotic treatments
As the intestinal microflora could be a causal triggering factor of metabolic diseases, Cani et al. [58] treated control, high-fat-fed and ob/ob mice with broad-spectrum antibiotics. They used ampicillin and neomycin as examples of antibiotics that are poorly absorbed (or unabsorbed in the case of neomycin) by the organism to reduce the occurrence of systemic effects [65]. The results showed that changes in the gut microbiota induced by antibiotic treatment reduced metabolic endotoxaemia and
Microflora as a friend
Mazmanian et al. [93] showed that a specific component of the intestinal microflora can directly interact with the innate immune system of the host, resulting in a beneficial effect. In their elegantly written report, the investigators showed that Bacteroides fragilis can protect animals against experimental colitis induced by Helicobacter hepaticus, a potential pathogenic commensal of the intestinal microflora. The benefit depends on the production of a single specific molecule produced by B.
Conflicts of interest
The authors have no conflicts of interest to declare in relation to this report.
References (93)
A dynamic partnership: celebrating our gut flora
Anaerobe
(2005)The indigenous gastrointestinal microflora
Trends Microbiol
(1996)- et al.
Developmental microbial ecology of the neonatal gastrointestinal tract
Am J Clin Nutr
(1999) Intestinal microflora
Gastroenterology
(1971)- et al.
The mucosal immune system at the gastrointestinal barrier
Best Pract Res Clin Gastroenterol
(2008) - et al.
Eubacterium limosum activates isoxanthohumol from hops (Humulus lupulus L) into the potent phytoestrogen 8-prenylnaringenin in vitro and in rat intestine
J Nutr
(2008) - et al.
Carbohydrate digestibility and metabolic effects
J Nutr
(2007) - et al.
Probiotics that modify disease risk
J Nutr
(2005) - et al.
Bacterial diversity in the human gut
Adv Appl Microbiol
(2004) Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream
Exp Hematol
(2002)
Host-bacterial coevolution and the search for new drug targets
Curr Opin Chem Biol
Mucosal flora in inflammatory bowel disease
Gastroenterology
NOD mouse colonies around the world--recent facts and figures
Immunol Today
Obesity: epidemiology and clinical aspects
Best Pract Res Clin Gastroenterol
Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene
J Biol Chem
Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding
Pathol Biol (Paris)
Chylomicrons promote intestinal absorption of lipopolysaccharides
J Lipid Res
Energy intake is associated with endotoxemia in apparently healthy men
Am J Clin Nutr
Impairment of the intestinal barrier by ethanol involves enteric microflora and mast cell activation in rodents
Am J Pathol
Glucagon-like peptide-1 and energy homeostasis
J Nutr
The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes
Lancet
Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics
J Nutr
Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin
J Nutr
Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease
Hepatology
Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells
J Hepatol
Feeding our immune system: impact on metabolism
Clin Dev Immunol
The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction
J Immunol
Role of mucosal dendritic cells in inflammatory bowel disease
World J Gastroenterol
Unraveling gut inflammation
Science
Unravelling the pathogenesis of inflammatory bowel disease
Nature
Influence of plant and bacterial myrosinase activity on the metabolic fate of glucosinolates in gnotobiotic rats
Br J Nutr
Metabolism of dietary soy isoflavones to equol by human intestinal microflora--implications for health
Mol Nutr Food Res
The gut flora as a forgotten organ
EMBO Rep
A microbial world within us
Mol Microbiol
Lactic acid bacteria and human health
Ann Med
The role of the intestinal microflora for the development of the immune system in early childhood
Eur J Nutr
Interactions among microorganisms of the indigenous intestinal flora and their influence on the host
Rev Infect Dis
Effect of the normal microbial flora on gastrointestinal motility
Proc Soc Exp Biol Med
Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells
Proc Natl Acad Sci U S A
Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora
Gut
Molecular analysis of commensal host-microbial relationships in the intestine
Science
Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis
Nature
Escherichia coli--a model system that benefits from and contributes to the evolution of proteomics
Biotechnol Bioeng
Metagenomic analysis of the human distal gut microbiome
Science
Development of the Human Infant Intestinal Microbiota
PLoS Biol
Diversity of the human intestinal microbial flora
Science
Cited by (67)
Food supplements could be an effective improvement of diabetes mellitus: a review
2021, Journal of Future FoodsThe Influence of Fiber on Gut Microbiota: Butyrate as Molecular Player Involved in the Beneficial Interplay Between Dietary Fiber and Cardiovascular Health
2017, Dietary Fiber for the Prevention of Cardiovascular Disease: Fiber's Interaction between Gut Micoflora, Sugar Metabolism, Weight Control and Cardiovascular HealthEnterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health
2017, Free Radical Biology and MedicineCitation Excerpt :Ecological conditions vary immensely along both the length of the GI tract as well as in cross-section from lumen to the mucosal brush-border [173,267,308,309]. Numerous facets of GI microbial community composition and metabolism have been associated with various disease states, including CVD, obesity, diabetes, and features of metabolic syndrome [274,310–313]. There are no studies that directly investigate an association between the gut microbiome, nitrate, and PH. However, several features common to gut dysbiosis, altered NO-signaling, and PH suggest a role in disease including inflammation and NO production.
A Metagenomic Insight into the Human Microbiome: Its Implications in Health and Disease
2016, Medical and Health Genomics