Secondary Logo

Journal Logo

Influence of high-fat diet on gut microbiota

a driving force for chronic disease risk

Murphy, E. Angela; Velazquez, Kandy T.; Herbert, Kyle M.

Current Opinion in Clinical Nutrition & Metabolic Care: September 2015 - Volume 18 - Issue 5 - p 515–520
doi: 10.1097/MCO.0000000000000209
NUTRITION AND THE GASTROINTESTINAL TRACT: Edited by M. Isabel T.D. Correia and Alastair Forbes
Free

Purpose of review This review will examine the recent scientific literature surrounding high-fat-diet (HFD)-induced alterations in gut microbiota and subsequent development of obesity and chronic disease risk.

Recent findings Excessive consumption of HFDs has undoubtedly contributed to the obesity epidemic. The mechanisms responsible for this relationship are, however, likely to be more complex than the simple concept of energy balance. In fact, emerging literature has implicated HFD-induced alterations in gut microbiota in the obesity epidemic. HFD consumption generally leads to a decrease in Bacteroidetes and an increase in Firmicutes, alterations that have been associated with obesity and subsequent development of chronic diseases. Potential mechanisms for this effect include an improved capacity for energy harvest and storage, and enhanced gut permeability and inflammation. We highlight the most important recent advances linking HFD-induced dysbiosis to obesity, explore the possible mechanisms for this effect, examine the implications for disease development, and evaluate the possibility of therapeutic targeting of the gut microbiome to reduce obesity.

Summary A better understanding of the mechanisms linking HFD to alterations in gut microbiota is necessary to allow for the regulation of dysbiosis and ensuing promotion of antiobesity effects.

Department of Pathology, Microbiology, and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, USA

Correspondence to E. Angela Murphy, Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, 6439 Garners Ferry Rd., Columbia, SC 29209, USA. Tel: +1 803 216 3414; fax: +1 803 216 3413; e-mail: Angela.Murphy@uscmed.sc.edu

Back to Top | Article Outline

INTRODUCTION

In the USA, it is estimated that 34.9% of the adult population is obese whereas 68.5% are classified as either overweight or obese [1]. This is of critical public health concern given the link between obesity and chronic diseases such as cancer, diabetes, cardiovascular disease, and central nervous system disorders. The global acceptance and widespread availability of energy dense foods along with the lack of physical activity are largely responsible for the dramatic increase in obesity rates. This may, however, present an oversimplistic view of this mechanism as it is now evident that the causes of obesity involve contributions from the environment and host genetics in addition to an imbalance between food intake and energy expenditure. As such, emerging evidence provides an argument for a role of the gut microbiome in the control of body weight and energy homeostasis. This is thought to be driven, at least in part, by high-fat-diet (HFD)-induced alterations in gut bacterial composition; HFD feedings have been associated with modifications in the gut microbial profile as well as decreased diversity [2,3]. This review will examine the recent literature on HFD-induced alterations in microbiota composition, the propensity for this to lead to an obese phenotype, the consequences for disease risk, and the potential to target HFD-induced dysbiosis for obesity prevention.

Box 1

Box 1

Back to Top | Article Outline

INFLUENCE OF HIGH-FAT-DIET ON DYSBIOSIS

The composition of gut microbiota is unique to each individual, is variable between persons, and is reasonably stable following the first year of life. Despite this, emerging literature implicates diet as an important influence on the gut microbial profile. As such, lack of adequate nutrition has been linked to dysfunctional microbiota and dysbiosis.

Recent research has focused on the influence of HFD consumption on gut microbial composition. For example, it has been reported that HFD promotes a decrease in Bacteroidetes and an increase in both Firmicutes and Protebacteria[2,3]. Similar phylum-level shifts were reported following high-fat and high-sucrose feedings [4]. Specifically, it was reported that body fat percentage growth was negatively associated with the abundance of Akkermansia (phylum Verrucomicrobia) but positively associated with the relative abundances of Lactoococcus from phylum Firmicutes and with the genera Allobaculum (phylum Bacteroidetes) [4]. Carmody et al.[5▪] used over 200 strains of mice to determine whether variations in gut microbiota are primarily driven by host genetics or by dietary factors. Their findings indicate that a high-fat and high-sugar diet reproducibly altered the gut microbiota despite differences in host genotype [5▪]. More specifically, the gut microbiota exhibited a linear dose response to dietary perturbations, taking an average of 3.5 days for each diet-responsive bacterial group to reach a new steady state [5▪]. However, repeated dietary shifts demonstrated that most changes to the microbiome are reversible, whereas the abundance of certain bacteria depends on prior consumption [5▪]. Arguably, the most convincing evidence for an impact of HFD-induced gut microbial changes in obesity comes from an investigation to determine whether shifts in the microbial profile during obesity are a characteristic of the phenotype or a consequence of obesogenic feeding [6▪▪]. Duca et al. reported that obese-prone rats display a gut microbiota distinct from obese-resistant rats fed the same HFD [6▪▪]. Transfer of obese-prone but not obese-resistant microbiota to germ-free mice replicated the characteristics of the obese-prone phenotype, increased weight gain and adiposity, intestinal permeability, and inflammation, and enhanced lipogenesis and adipogenesis [6▪▪]. Interestingly, HFD-induced changes in gut microbiota and resulting metabolic perturbations appear to be dependent on the fat content as milk fat-based, lard-based (saturated fatty acid sources), or safflower oil (polyunsaturated fatty acid)-based HFDs induced dramatic and specific 16S rRNA phylogenic profiles that were associated with different inflammatory and lipogenic mediator profiles of mesenteric and gonadal fat depots [7]. Not all the data, however, support a positive association as a few studies have reported that the absence of intestinal microbiota does not protect mice from diet-induced obesity [8]. Inconsistencies in the literature are likely because, at least in part, of microbial adaptation to diet and time [9].

Back to Top | Article Outline

MECHANISMS LINKING HIGH-FAT-DIET-INDUCED DYSBIOSIS TO OBESITY

The consequences of HFD-induced dysbiosis are potentially significant as the majority of evidence links this to the promotion of obesity and ensuing metabolic disorders. For example, in a study of obese and overweight individuals, it was reported that reduced microbial richness was associated with more pronounced dys-metabolism [10]. Potential mechanisms for this effect include an improved capacity for energy harvest and storage, and enhanced gut permeability and inflammation.

Back to Top | Article Outline

Improved capacity for energy harvest and energy storage

It has been reported that the microbiome from an obese mouse has an increased capacity to harvest energy from the diet [11]. This trait is transmissible as colonization of germ-free mice with an ‘obese microbiota’ results in an increase in body fat compared with colonization with a ‘lean microbiota’ [11]. This phenomenon is reportedly because of fermentation of undigested food components by gut microbes leading to increased short-chain fatty acids (SCFAs), an important energy source for the host [12]. In support of this, Schwiertz et al.[13] found significant differences in SCFA concentrations between lean and obese individuals. Similarly, overweight/obese women with metabolic disorder had a higher proportion of bacteria belonging to Eubacterium rectale–Clostridium coccoides, a bacterium associated with efficient energy harvest from nutrients in the gut, than overweight/obese women without metabolic disorder and normal weight women [14].

In addition, gut microbiota reportedly play a role in the modulation of genes associated with fat storage. Conventionalization of germ-free mice with a normal microbiota produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. A decrease in fasting-induced adipocyte factor is thought to play a role in this process as it is selectively suppressed in the intestinal epithelium of normal mice by conventionalization, and studies using knockout mice show that it is necessary for the microbiota-induced deposition of triglycerides in adipocytes [15]. Similarly, adenosine monophosphate-activated protein kinase is thought to influence fat storage as germ-free mice consuming a Western-style diet have increased levels of adenosine monophosphate-activated protein kinase and its downstream targets involved in fatty acid oxidation in the skeletal muscle and liver compared with conventionalized mice [16].

Back to Top | Article Outline

Enhanced gut permeability and inflammation

HFD-induced obesity is associated with low-grade chronic inflammation. The initiating events for this process are thought to be because of an increase in intestinal lipopolysaccharide (LPS)-bearing bacterial species and subsequent activation of Toll-like receptors (TLRs) on immune cells [17]. Further, HFD can alter intestinal barrier structure via a reduction of tight junction proteins [18]. An increase in bacterial translocation ensues leading to elevations in circulating LPS and metabolic endotoxemia [17]. A study [19] by Burcelin's group reported that HFD modulates gut microbiota in association with increased plasma LPS. Interestingly, when antibiotic treatment was used to deplete gut microbiota, plasma LPS as well as cecal LPS was reduced and this was associated with reduced glucose intolerance, body weight gain, fat mass development, increased inflammation, and macrophage accumulation [19]. Similarly, Ding et al.[20] reported an increase in inflammatory mediators in the ileum and colon of mice following HFD feedings in conventionally raised mice but not in germ-free mice. Interestingly, these effects preceded weight gain and obesity and showed strong and significant associations with progression of obesity and development of insulin resistance [20]. In addition, rats that exhibited an obesity-prone phenotype following HFD feedings showed an increase in TLR4 activation, ileal inflammation, intestinal permeability, and plasma LPS, but these effects were not reported for obesity-resistant rats [21]. Further, an increase in Enterobacteriales was reported in the obese-prone rats, which is known to be associated with inflammation [21].

Back to Top | Article Outline

HIGH-FAT-DIET-INDUCED DYSBIOSIS AND DISEASE RISK

Obesity has been associated with cancer, diabetes, cardiovascular disease, and central nervous system disorders to name a few. The mechanisms that link obesity to disease risk are undoubtedly multifactorial in origin. Recent evidence, however, provides a compelling argument to include gut microbiota as a potential player.

Back to Top | Article Outline

Cancer

Recent studies provide evidence to support a role of the gut microbiome in driving obesity-induced cancers. For example, Schulz et al.[22▪▪] examined the effects of HFD on tumor progression in the small intestine using a genetically susceptible K-rasG12Dint mouse model and found a shift in the composition of the gut microbiota, which was associated with increased tumor progression. The transfer of fecal samples from HFD-fed mice with intestinal tumors to healthy K-rasG12Dint mice resulted in enhanced tumorigenesis, whereas the use of antibiotics blocked this effect, directly implicating microbiota in disease progression [22▪▪]. These effects occur independent of obesity as the K-rasG12Dint mice were resistant to HFD-induced obesity [22▪▪]. Similarly, Yoshimoto et al.[23] reported that both HFD-induced and genetic obesity causes alterations in gut microbiota leading to increased deoxycholic acid, a gut bacterial metabolite known to cause DNA damage. Enterohepatic circulation of deoxycholic acid resulted in secretion of various inflammatory and tumor-promoting factors in the liver, thus facilitating chemically induced hepatocellular carcinoma development in mice [23].

Back to Top | Article Outline

Cardiovascular disease

Current literature supports an influence of gut microbiota on cardiovascular disease. This is thought to occur via sensing of gut microbial-derived products by the host receptor system [24]. Li et al. reported that a ‘Western-type’ diet induced atherosclerosis progression in association with altered gut microbiota functions among others. Switching to a normal diet reversed this process implicating a crucial role of gut microbiota in atherosclerosis development [25]. In addition, it was reported that atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota and that this may be influenced by intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide [26▪]. Similarly, Ghosh et al.[27] treated LDLR-deficient mice with antibiotics and reversed the effects of a Western diet on development of atherosclerosis. A human study found that bacteria from the oral cavity and the gut correlated with plasma cholesterol levels and may correlate with disease markers of atherosclerosis [28]. Likewise, Karlsson et al.[29] reported that patients with symptomatic atherosclerosis harbor characteristic changes in the gut metagenome.

Back to Top | Article Outline

Diabetes

It is well recognized that obesity can lead to diabetes; thus it is no surprise that studies have examined a link between HFD-induced dysbiosis and insulin resistance. Mice fed a HFD that were classified as diabetic or diabetic resistant displayed a gut microbial profile specific to each metabolic phenotype despite having the same background and nutritional status [30]. These findings were consistent in humans as insulin-resistant versus insulin-sensitive obese patients had a segregated microbial DNA profile on the basis of their degree of insulin action [31]. In an effort to find bacterial predictors of type-2 diabetes, it was discovered that blood levels of 16S rDNA are elevated well before development of diabetes [32]. Mechanistic support for this relation comes from antibiotic treatment in HFD fed mice in which reduced levels of fasting glucose and insulin and improved glucose and insulin tolerance were reported [33]. A recent study by Denou et al.[34▪] reported that NOD2 plays a role in this process as defective NOD2 peptidoglycan sensing promotes dysbiosis and insulin resistance. Similarly, the SCFA receptor GPR43 is likely to be involved as it has been reported that the gut microbiota suppresses insulin-mediated fat accumulation via this receptor [35].

Back to Top | Article Outline

Central nervous system disorders

Accruing evidence indicates that the gut microbiota can communicate with the central nervous system, thus influencing brain function and behavior. Germ-free mice display increased motor activity and reduced anxiety behavior in conjunction with altered expression of associated genes [36]. Hsiao et al. demonstrated microbial alterations in a mouse model that is known to display features of autism spectrum disorder. Interestingly, treatment of these mice with the human commensal Bacteroides fragilis ameliorates the defects in communicative, stereotypic, anxiety-like, and sensorimotor behaviors [37]. Additionally, disruption of the gut microbiota in early life selectively affects visceral pain in male rats [38]. A recent study [39] of Parkinson's patients indicated that the intestinal microbiome is altered in Parkinson's disease and is related to motor phenotype. Although it is clear that gut microbiota can influence central nervous system disorders, studies implicating HFD-induced microbiome alterations in this process are currently limited. A study by Bruce-Keller et al.[40▪], however, reported that mice transplanted with microbiota from HFD-fed mice had significant selective disruptions in exploratory, cognitive, and stereotypical behavior in association with increased neuroinflammation and disrupted cerebrovascular homeostasis.

Back to Top | Article Outline

TARGETING HIGH-FAT-DIET-INDUCED DYSBIOSIS FOR OBESITY PREVENTION

Recent studies have evaluated the possibility of therapeutic targeting of the gut microbiome to reduce obesity. Although still in its infancy, several studies have reported promising findings.

The majority of studies to date have employed probiotics to target HFD-induced dysbiosis. For example, Stenman et al.[41] treated HFD-fed mice with Bifidobacterium animalis ssp. lactis 420 and found a decrease in fat mass along with improved glucose tolerance, decreased LPS levels, and reduced inflammation. Similarly, Saccharomyces boulardii Biocodex, a probiotic yeast, reduced body weight, fat mass, hepatic steatosis, and inflammatory tone in leptin-resistant obese and type-2 diabetic mice in accordance with dramatic changes in the gut microbial composition [42]. In another study [43], the prebiotic oligofructose, reduced energy intake, weight gain and fat mass, and both oligofructose and the probiotic Bifidobacterium animalis subsp. lactis BB12 improved glycemia. Park et al.[44] reported that HFD-fed mice treated with Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 had reduced weight gain and fat accumulation as well as lowered plasma insulin, leptin, total cholesterol, and liver toxicity biomarkers, which was associated with changes in gut bacterial composition and diversity. Although Lactobacillus salivarius UCC118 Bac(+) changed the microbiome composition in HFD-induced obese mice, this was not reflected by an improvement in the metabolic profile [45]. In a follow-up time course study [46], this group, however, reported that Lactobacillus salivarius UCC118 Bac(+) does, in fact, result in a decrease in weight gain, but the effects appear to be time dependent.

Recent evidence supports a possible beneficial effect of plant components in altering gut microbial composition in obesity models. Quercetin, but not resveratrol, was effective at reducing dysbiosis induced by a high-fat sucrose diet [47]. Although this was associated with reduced serum insulin and insulin resistance, these effects were also reported for resveratrol that scarcely modified the profile of gut bacteria [47]. Similarly, fermented green tea extract was reported to alter the composition of gut microbiota, and this was linked to a decrease in fat mass, reduced inflammation, and alleviation of glucose intolerance [48]. Further, a polyphenol-rich cranberry extract was reported to protect mice from diet-induced obesity and metabolic perturbations, which was associated with a proportional increase in Akkermansia spp. population [49].

Back to Top | Article Outline

CONCLUSION

Although it is clear that HFD can result in significant changes in gut microbial composition, a large number of studies to date are simply associations between HFD consumption, altered gut bacterial composition, and promotion of obesity. Significant mechanistic research is needed to link specific gut phylotypes to obesity traits and subsequent risk for chronic disease. Although the available literature on therapeutic targeting of the microbiota to counteract diet-induced obesity appears promising, whether this presents a realistic approach is unclear. Viable agents have yet to be fully recognized, and specifics on the dose, timing, and frequency of administration are still unknown.

Back to Top | Article Outline

Acknowledgements

None.

Back to Top | Article Outline

Financial support and sponsorship

This work was supported by grants awarded to E.A.M. from the National Cancer Institute (R21CA167058 and R21CA175636), the National Center for Complementary and Alternative Medicine (K01AT007824), and the University of South Carolina [Advanced Support Programs for Innovative Research Excellence (ASPIRE)].

Back to Top | Article Outline

Conflicts of interest

There are no conflicts of interest.

Back to Top | Article Outline

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
Back to Top | Article Outline

REFERENCES

1. Ogden CL, Carroll MD, Flegal KM. Prevalence of obesity in the United States. JAMA 2014; 312:189–190.
2. Zhang C, Zhang M, Pang X, et al. Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J 2012; 6:1848–1857.
3. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 2009; 137:1716–1724.
4. Parks BW, Nam E, Org E, et al. Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice. Cell Metab 2013; 17:141–152.
5▪. Carmody RN, Gerber GK, Luevano JM Jr, et al. Diet dominates host genotype in shaping the murine gut microbiota. Cell Host Microbe 2015; 17:72–84.

This study evaluated whether variations in gut microbiota were primarily driven by host genetics or dietary factors. Their findings emphasized the dominant role that diet played in shaping interindividual variations in host-associated microbiota communities.

6▪▪. Duca FA, Sakar Y, Lepage P, et al. Replication of obesity and associated signaling pathways through transfer of microbiota from obese-prone rats. Diabetes 2014; 63:1624–1636.

This investigation sought to determine whether shifts in the microbial profile during obesity were a characteristic of the phenotype or a consequence of obesogenic feeding. Their findings indicated that obesity was characterized by an unfavorable microbiome predisposing the host to inflammation, weight gain, and adiposity.

7. Huang EY, Leone VA, Devkota S, et al. Composition of dietary fat source shapes gut microbiota architecture and alters host inflammatory mediators in mouse adipose tissue. JPEN J Parenter Enteral Nutr 2013; 37:746–754.
8. Fleissner CK, Huebel N, Abd El-Bary MM, et al. Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr 2010; 104:919–929.
9. Murphy EF, Cotter PD, Healy S, et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 2010; 59:1635–1642.
10. Cotillard A, Kennedy SP, Kong LC, et al. Dietary intervention impact on gut microbial gene richness. Nature 2013; 500:585–588.
11. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444:1027–1031.
12. Backhed F, Ley RE, Sonnenburg JL, et al. Host-bacterial mutualism in the human intestine. Science 2005; 307:1915–1920.
13. Schwiertz A, Taras D, Schafer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity 2010; 18:190–195.
14. Munukka E, Wiklund P, Pekkala S, et al. Women with and without metabolic disorder differ in their gut microbiota composition. Obesity 2012; 20:1082–1087.
15. Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 2004; 101:15718–15723.
16. Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 2007; 104:979–984.
17. Kim KA, Gu W, Lee IA, et al. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One 2012; 7:e47713.
18. Shen W, Wolf PG, Carbonero F, et al. Intestinal and systemic inflammatory responses are positively associated with sulfidogenic bacteria abundance in high-fat-fed male C57BL/6J mice. J Nutr 2014; 144:1181–1187.
19. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57:1470–1481.
20. Ding S, Chi MM, Scull BP, et al. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 2010; 5:e12191.
21. de La Serre CB, Ellis CL, Lee J, et al. Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 2010; 299:G440–G448.
22▪▪. Schulz MD, Atay C, Heringer J, et al. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature 2014; 514:508–512.

This investigation examined the link between high-fat-diet, dysbiosis, and intestinal carcinogenesis. The findings indicated that high-fat-diet promoted tumorigenesis, independent of obesity, and this was mediated by interactions between host factors and the microbial community.

23. Yoshimoto S, Loo TM, Atarashi K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013; 499:97–101.
24. Brown JM, Hazen SL. The gut microbial endocrine organ: bacterially derived signals driving cardiometabolic diseases. Annu Rev Med 2015; 66:343–359.
25. Li D, Zhang L, Dong F, et al. Metabonomic changes associated with atherosclerosis progression for LDLR mice. J Proteome Res 2015; 14:2237–2254.
26▪. Gregory JC, Buffa JA, Org E, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem 2015; 290:5647–5660.

This investigation reported that atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. These findings were linked to intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide.

27. Ghosh SS, Bie J, Wang J, Ghosh S. Oral supplementation with nonabsorbable antibiotics or curcumin attenuates Western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice: role of intestinal permeability and macrophage activation. PLoS One 2014; 9:e108577.
28. Koren O, Spor A, Felin J, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A 2011; 108 (Suppl 1):4592–4598.
29. Karlsson FH, Fak F, Nookaew I, et al. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 2012; 3:1245.
30. Serino M, Luche E, Gres S, et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 2012; 61:543–553.
31. Serino M, Fernandez-Real JM, Garcia-Fuentes E, et al. The gut microbiota profile is associated with insulin action in humans. Acta Diabetol 2013; 50:753–761.
32. Serino M, Blasco-Baque V, Burcelin R. Microbes on-air: gut and tissue microbiota as targets in type 2 diabetes. J Clin Gastroenterol 2012; 46 (Suppl):S27–S28.
33. Carvalho BM, Guadagnini D, Tsukumo DM, et al. Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia 2012; 55:2823–2834.
34▪. Denou E, Lolmede K, Garidou L, et al. Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance. EMBO Mol Med 2015; 7:259–274.

This study examined the role of NOD2 in metabolic inflammation and insulin sensitivity in high-fat-diet-fed mice. Their findings indicated that an intact bacterial cell wall peptidoglycan NOD2 sensing system regulated gut mucosal bacterial colonization and a metabolic tissue dysbiosis that was a potential trigger for increased metabolic inflammation and insulin resistance.

35. Kimura I, Ozawa K, Inoue D, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nature Commun 2013; 4:1829.
36. Diaz Heijtz R, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 2011; 108:3047–3052.
37. Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 2013; 155:1451–1463.
38. O’Mahony SM, Felice VD, Nally K, et al. Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats. Neuroscience 2014; 277:885–901.
39. Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord 2015; 30:350–358.
40▪. Bruce-Keller AJ, Salbaum JM, Luo M, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry 2015; 77:607–615.

This study reported that mice transplanted with microbiota from high-fat-diet-fed mice had significant selective disruptions in exploratory, cognitive, and stereotypical behavior in association with increased neuroinflammation and disrupted cerebrovascular homeostasis.

41. Stenman LK, Waget A, Garret C, et al. Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice. Beneficial Microbes 2014; 5:437–445.
42. Everard A, Matamoros S, Geurts L, et al. Saccharomyces boulardii administration changes gut microbiota and reduces hepatic steatosis, low-grade inflammation, and fat mass in obese and type 2 diabetic db/db mice. MBio 2014; 5:e01011–e1014.
43. Bomhof MR, Saha DC, Reid DT, et al. Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats. Obesity 2014; 22:763–771.
44. Park DY, Ahn YT, Park SH, et al. Supplementation of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One 2013; 8:e59470.
45. Murphy EF, Cotter PD, Hogan A, et al. Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut 2013; 62:220–226.
46. Clarke SF, Murphy EF, O'Sullivan O, et al. Targeting the microbiota to address diet-induced obesity: a time dependent challenge. PLoS One 2013; 8:e65790.
47. Etxeberria U, Arias N, Boque N, et al. Shifts in microbiota species and fermentation products in a dietary model enriched in fat and sucrose. Benef Microbes 2015; 6:97–111.
48. Seo DB, Jeong HW, Cho D, et al. Fermented green tea extract alleviates obesity and related complications and alters gut microbiota composition in diet-induced obese mice. J Med Food 2015; 18:549–556.
49. Anhe FF, Roy D, Pilon G, et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut 2015; 64:872–883.
Keywords:

chronic disease; gut microbiome; high-fat-diet; obesity

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.