obesity is a major public health concern 
 affecting both the developed and the developing world . the obesity epidemic started 
 to grow in us in the 1980s , with values rising from 22.9% obese adults in 19881994 to 30.5% in 19992000 . in 1996 , the world health organization ( who ) together with 
 national ministries of health agreed to tackle obesity worldwide , but since 
 then it has increased sharply , reaching values of at least 20% obese adults in 
 most us 
  states and european countries . obesity is detrimental to the quality of life and implies 
 high health costs as a consequence of its associated morbidities . overweight 
 and obesity constitute risk factors for a number of chronic diseases 
 including diabetes , cardiovascular diseases , 
 nonalcoholic fatty liver disease , cancer , and other immune - related disorders 
 such as asthma and infections . obesity results from a long - term positive 
 imbalance between energy intake and expenditure with excessive increase in body 
 fat . obesity and the associated disorders are also characterized by a state of 
 chronic , low - grade inflammation with abnormal cytokine and adipokine production 
 . production of inflammatory immune mediators such as tumor - necrosis factor 
 ( tnf)- , interleukin ( il)-6 , il-1 , cc - chemokine ligand 2 ( ccl2 or monocyte chemotactic protein 1 ) , and the 
 proinflammatory adipokines leptin and resistin is usually high in these subjects , 
 whereas production of the anti - inflammatory and insulin - sensitizing adipokine 
 adiponectin is reduced . inflammation associated with obesity involves 
 diverse signal transduction cascades including the nuclear factor kappa b ( nf-b)/ikk system and the jun n - terminal kinase ( jnk ) [ 4 , 6 ] . leptin is the dominant long - term signal informing the brain of energy 
 stores and , together with insulin , is secreted upon ingestion thus inhibiting 
 food intake . however , human obesity is not commonly associated with 
 leptin - deficiency but with leptin - resistance and increased levels of this 
 adipokine . leptin seems to exert a proinflammatory effect by inducing the 
 production of ccl2 , proinflammatory cytokines ( tnf- , il-6 , and il-12 ) , and also typical t helper ( th ) 1-cytokines ( il-2 and ifn ) involved in other chronic inflammatory and 
 autoimmune disorders such as crohn 's disease [ 6 , 7 ] . although susceptibility to definitive increases 
 in body weight is genetically determined , the environment also influences weight 
 gain considerably . it is currently believed that macrosocial changes associated 
 with regular intake of energy - dense foods and low - physical activity have 
 created an obesogenic environment worldwide , 
 constituting the cornerstone of the global obesity epidemic . traditional treatments based on calorie - restricted diets and increased physical 
 activity have succeeded in controlling obesity to some extent . nevertheless , these strategies usually yield limited 
 and short - lived weight reductions and most people regain some of their weight 
 loss . neither has pharmacological therapy fully succeeded in effectively 
 treating obesity for long - term periods and also has a number of side - effects [ 3 , 10 ] . in this scenario , the identification of additional environmental factors 
 involved in energy regulation is critical with a view to develop more efficient 
 intervention strategies . the human gut is populated by an array of 
 bacterial species that coevolve with the host since birth and maintain dynamic 
 interactions with each other throughout life . the collective genome 
 ( microbiome ) of the gut microbiota contains at least 100 times as many genes as 
 the human genome , with most serving human physiological functions . the metabolic role of the gut microbiota is 
 essential to the biochemical activity of the human body , resulting in salvage 
 of energy , generation of absorbable compounds , and production of vitamins and 
 other essential nutrients . thus , humans are considered superorganisms 
 whose metabolism represents the combination of both microbial and human 
 features . the gut microbiota also regulates many aspects of innate and 
 acquired immunity , protecting the host from pathogen invasion and chronic 
 inflammation [ 13 , 14 ] . in contrast , imbalances in the composition of gut 
 microbiota have been associated with susceptibility to infections , immune - based 
 disorders , and recently also with insulin resistance and body weight gain . 
 in the last decades , sound relationships between the composition of the gut 
 microbiota and human health have been established , leading to the design of 
 dietary strategies to favor the prevalence of beneficial bacteria to maintain a 
 healthy status . these strategies include the administration of prebiotic 
 oligosaccharides , which stimulate the growth and/or metabolic activity of 
 beneficial bacteria , and also of selected bacterial strains ( probiotics ) in the 
 form of functional foods and supplements . herein , the current knowledge of 
 the relationships between the composition and functions of the gut microbiota 
 and obesity is reviewed , including some studies intended to evaluate the 
 effects of probiotics and prebiotics in the management of metabolic disorders . obesity has been associated with increases in 
 the relative abundance of firmicutes and proportional reductions in bacteroidetes by comparisons between the distal gut microbiota of genetically obese ( leptin 
 deficient ob / ob mice ) and lean mice , as well as of that of obese and lean human 
 subjects [ 17 , 18 ] . in addition , obese human adults submitted to a hypocaloric 
 diet ( either low carbohydrate- or low fat - containing diet ) showed significant 
 increases in fecal proportions of bacteroidetes paralleled to weight loss over a one - year - long intervention in a few subjects ; 
  nonetheless , species diversity was reported to remain constant . studies on the 
 cecal microbiota of genetically obese mice and their lean littermates also 
 related a higher proportion of archaea to obesity . these relationships between obesity and the gut microbiota 
 composition were first based on dna sequence analysis of the total distal gut 
 microbiome of mice and humans obtained from genomic libraries or directly by 
 pyrosequencing . of these microbial groups , bacteroidetes and firmicutes constitute the 
 dominant bacterial subdivision ( > 99% ) among the 70 bacterial subdivisions identified 
 in distal gut , while methanobrevibacterium 
 smithii constitutes the most prominent methanogenic archaeon among the 13 archaea divisions reported to date based 
 on 16s ribosomal dna sequencing data . more recently , diet - induced obesity 
 in animal models has been associated with increases in the proportion of a 
 single - uncultured clade within the mollicutes class of firmicutes , which was also 
 diminished by subsequent dietary manipulations to limit weight gain , showing 
 more specific relationships between obesity and components of the gut 
 microbiota . a study of a chinese family , comprising 3 males and 4 females , 
 also related the lowest bacteroidetes to firmicutes ratio to the overweight 
 individual , and demonstrated a high degree of interpersonal variation in this 
 value , ranging from 0.26 to 1.36 . differences in fecal microbiota composition 
 were shown to predict overweight in children early in life . children maintaining 
 normal weight showed a greater number of bifidobacteria , while children 
 becoming overweight showed a greater number of staphylococcus aureus in feces during infancy . although the 
 selected population group included children prone to allergy , who may show the 
 described microbial aberrancies , the obtained results are also in accordance 
 with the protective role attributed to breast - milk against developing obesity 
 later in life , and the predominance of bifidobacteria in the 
 gut of breastfed babies . shifts in composition of animal and human gut 
 bacteria in response to dietary changes ( a high protein / low carbohydrate or 
 high - fat intake ) have also been shown to alter microbial composition and 
 activity in the large intestine that , in turn , could exert an impact on health [ 15 , 24 ] . obese humans submitted to a dietary intervention , based on reducing 
 carbohydrate intake and increasing protein intake , showed reductions in 
 populations of bifidobacterium , and roseburia spp . and eubacterium rectale subgroups of clostridial cluster xiva when 
 carbohydrate intake was decreased , while no differences were detected in bacteroides or other clostridial 
 clusters . the abundance of roseburia spp . and e. rectale group 
 correlated well with the decline in fecal butyrate as carbohydrate intake was 
 reduced ; however , relationships to body weight were not established . recent 
 studies on the evolution of mammals and their gut microbes pointed out that the 
 acquisition of a new diet is a fundamental driver for changes in gut bacterial 
 diversity , which increases from carnivory to omnivory to herbivory . alterations 
 in gut microbiota composition associated with genetic or diet - induced obesity 
 have also been shown to be reversible by oral transfer of the gut microbiota 
 from lean mice to a germ - free recipient [ 19 , 26 ] or by administration of 
 prebiotic substrates to animal models at least over short - term periods . therefore , it seems likely that a combination of environmental ( e.g. diet ) and genetic factors contributes to defining unique 
 combinations of bacteria within an individual , which could favor either an 
 obese or lean phenotype . in this context , some authors argue that both antibiotics 
 and probiotics have demonstrated to act as growth promoters when used in animal 
 feeding and , therefore , could contribute to current human obesity . therefore , their common effect on animal weight gain can 
 be only a consequence of their common role in preventing infections . by 
 contrast , other scientists consider that the intentional manipulation of the 
 composition of gut microbiota via dietary strategies is a possible tool to 
 revert or prevent overweight and particularly metabolic - associated disorders 
 [ 19 , 26 , 27 ] . although this line of research is still in its infancy , in the 
 following sections we summarize current evidence on the mechanisms of action of 
 gut microbiota on metabolic and immune aspects of obesity and the consequences 
 of its dietary manipulation by pro- and prebiotics . the gut microbiota is considered a critical 
 factor , together with lifestyle , involved in energy metabolism and obesity . germ - free mice colonized by the distal gut microbiota of conventionally raised 
 mice produced a remarkable increase ( 60% ) in body fat within 1014 days , although 
 feed consumption was reduced compared to the control germ - free mice . this process also stimulated the synthesis of 
 leptin , and produced faster glycemia and insulinemia , paralleled to body - fat 
 increase . the microbial colonization was demonstrated to increase the 
 host 's ability to both harvest energy from the diet and store this energy in 
 adypocites . this is thought to be achieved by diverse mechanisms including 
 improvement of diet macronutrient utilization , generation of metabolites 
 involved in energy balance and regulation of host gene expression . commensal 
 bacteria have specialized sets of hydrolyses and transporters to digest 
 nutrients , like complex polysaccharides , that would , otherwise , be inaccessible 
 to humans . these are the main energy sources for bacteria colonizing the large 
 intestine and confer them a competitive advantage over transient bacteria . the 
 microbial fermentation of undigested dietary compounds can provide 
 approximately 10% of the daily energy supply in omnivores and up to 70% in 
 herbivores . the degradation of matrix and other dietary polysaccharides 
 ( xylans , manans , pectins , starch , and inulin ) as well as host mucins lead   to 
 the generation of intermediate products ( lactate , succinate , etc . ) and finally 
 short - chain fatty acids ( scfa ) , including butyrate , acetate , and propionate , 
 which are almost completely absorbed along the gastrointestinal tract ( figure 1 ) . the ability to degrade highly insoluble polymeric substrates , such as 
 cellulose and mucin , seems to be limited to a subset of primary microbe 
 degraders in the large intestine and requires the expression of specific 
 substrate attachment , degradation , and uptake systems like the so - called 
 cellulosome complex . in fact , cellulolytic species have been shown to form 
 biofilm associations with plant surfaces in 
 vitro , integrated by a higher fraction of firmicutes and a smaller fraction of bacteroides , which suggests 
 a more prominent role of the former bacterial group in energy harvest from the 
 diet by facilitating complex polysaccharide utilization . several 
 clostridial clusters of firmicutes are important butyrate - producing bacteria in the distal gut , such as roseburia , e. rectale , eubacterium halli , and anaerostipes caccae , most of 
 which are included in clostridial cluster xiva . acetogenesis is another 
 metabolic attribute of relevance to obesity identified in this clostridial 
 cluster , which could partly explain the inverse relationship between firrmicutes and body weight reductions 
 in previous human intervention studies . soluble and less complex 
 oligosaccharides such as starch and fructooligosaccharides can be utilized by 
 other gut microbes such as bacteroides and bifidobacterium , which could also 
 contribute to the generation of intermediary metabolites and finally to scfa 
 ( figure 1 ) . although butyrate - producing bacteria would 
 appear to be related to higher gut metabolic   activity leading to overweight , butyrate is 
 extensively utilized by enterocytes and generally regarded as a healthy metabolite 
 . the main role of butyrate is to fuel enterocytes , covering up to 70% of their energy needs and contributing to 
 epithelial cell growth regulation and differentiation ( figure 1 ) . butyrate also 
 exerts anti - inflammatory effects and seems to contribute to glucagon - like 
 peptide 1 ( glp-1 ) generation , which is involved in satiety , by promoting 
 differentiation of stem cells into positive glp-1 l cells . altogether , this may 
 have beneficial effects on obese - prone subjects [ 32 , 33 ] . unlike butyrate , acetate 
 and propionate generated in intestinal lumen can reach the blood stream and the 
 liver through the portal vein ( figure 1 ) . acetate can contribute to lipid and 
 cholesterol synthesis in the liver by activating the cytosolic acetyl s coa 
 synthetase 2 , while propionate may inhibit lipid synthesis from acetate at least in rat hepatocytes . in fact , high - propionate production through 
 fermentation of starch or fructans has been associated with serum and liver 
 cholesterol reduction in rats and the acetate to propionate ratio in portal 
 blood , proposed as a possible maker of the effects of these dietary ingredients 
 on lipid metabolism [ 35 , 36 ] . nevertheless , acetate administered at a high dose 
 to rats and rat hepatocytes also induced amp kinase and/or reduced srebp-1c 
 expression related to lipogenesis inhibition , therefore further studies should 
 be carried out in humans to verify its positive or negative influences on lipid 
 metabolism . in addition to scfa , hydrogen is produced by polysaccharide - degrading 
 species and its further utilization by methanogens , acetogens and sulfate - reducing 
 gut microbes also activates the metabolism and growth of 
   polysaccharide - degrading 
 bacteria   ( figure 1 ) . archaea , which 
 are the main gut methanogenic microorganisms , were also overrepresented in 
 genetically obese mice as compared to their lean littermates and were related 
 to a greater capacity to promote adiposity when transferred to germ - free 
 recipients . eubacterium dolichum , 
 a human mollicute , was also shown to 
 favor import and processing of simple sugars in subjects under a western - style 
 diet , partly explaining its association and that of firmicutes division with obesity . in addition , cross - feeding 
 mechanisms between components of the gut microbiota have been identified at 
 different stages of the utilization of complex energy - rich polysaccharides . thus , b. adolescentis can degrade 
 starch , generating intermediate products ( lactate and acetate ) that can be 
 utilized by butyrate - forming bacteria such as e. hallii to generate butyrate   or by other intestinal 
 bacterial groups that convert lactate into propionate by the acrylate pathway . coinoculation of m. smithii and b. thetaiotaomicron into germ - free mice 
 showed that m. smithii directs b. thetaiotaomicron to focus on 
 fermentation of dietary fructans to acetate , whereas b. thetaiotaomicron - derived formate is used by m. smithii for methanogenesis . smithii cocolonization produced a 
 significant increase in host adiposity compared with monoassociated , or b. thetaiotaomicron - d . these studies emphasize the role of interactive sets 
 of microbes , rather than the role of individual microorganism within the gut 
 ecosystem in energy - metabolism and body weight regulation . this makes it far 
 more complex to identify those that are critical to obesity control through dietary 
 strategies . the gut microbiota may also influence energy 
 balance by modifying gene expression of host - related metabolic functions . angiogenesis , which is primarily involved in distributing nutrients to 
 peripheral tissues , was shown to depend on the gut microbial colonization 
 process . although capillary network 
 formation was arrested in adult germ - free mice , this developmental process 
 restarted and was completed within 10 days after colonization with a complete 
 microbiota harvested from conventionally raised 
 mice , or with bacteroides 
 thetaiotaomicron . commensal bacteria , such as b. thetaiotaomicron , have also been shown to induce expression of host 
 monosaccharide transporters in monocolonized mice . this would lead to 
 increasing the absorption of monosaccharides and scfa and , thereby , promote the novo synthesis of lipids in the 
 liver . in addition , the microbial colonization of germ - free mice increased 
 liver expression of two key enzymes involved in the de novo fatty acid 
 biosynthetic pathways , acetyl - coa carboxylase   and fatty acid synthase , as well as 
 the transcriptional factors chrebp and srebp-1 , which are involved in 
 hepatocyte lipogenic responses to insulin and glucose . unlike colonized mice , germ - free animals were 
 protected against the obesity that develops after consuming a western - style , 
 high - fat , sugar - rich diet by increasing fatty acid metabolism via two 
 complementary mechanisms : ( i ) increasing levels of circulating fasting - induced 
 adipose factor ( fiaf ) , which inhibits lipoprotein lipase thereby limiting fat 
 storage in adipocytes and promoting fat oxidation in muscle ; and ( ii ) 
 increasing skeletal muscle and liver levels of phosphorylated amp - activated 
 protein kinase and its downstream targets , involved in fatty acid    oxidation 
 . commensal gut microbiota and probiotics could 
 also regulate serum lipids by taking part in bile acid metabolism . bile salts 
 are highly effective detergents that promote solubilization and 
 absorption of dietary lipids throughout the intestine . the major 
 bile salt modifications of microbial origin in the human gut 
 include deconjugation , 
 oxidation of diverse hydroxyl groups and 7 /-dehydroxylation . certain probiotics 
 have been shown to decrease serum cholesterol levels by means of 
 their bile salt hydrolytic activity . significant bile salt 
 hydrolysis occurring in the proximal and terminal ileum reduces bile salt 
 uptake through high - affinity transport system and lipid 
 solubilization . this also leads to an increase in bile - acid excretion in feces 
 and bile - acid synthesis from cholesterol . for example , administration of l. acidophilus atcc 43121 seemed to reduce 
 serum cholesterol levels by bile acid deconjugation and dehydroxylation 
 reactions during cholesterol metabolism in hypercholesterolemia - induced rats . this intervention resulted in increased excretion of total fecal acid sterols 
 and secondary bile acids ( deoxycholic and lithocholic acids ) , and a reduction 
 of primary bile acids ( cholic and chenodeoxycholic acids ) . particularly , the 
 reduction in blood cholesterol levels was related to the increase in the 
 insoluble bile acid , lithocholic acid . more recently , metabolomic studies have 
 indicated that supplementation of lactobacillus 
 paracasei ncc2461 or lactobacillus 
 rhamnosus ncc4007 probiotics to germ - free mice colonized with human baby 
 flora - induced changes in hepatic - lipid metabolism and enterohepatic 
 recirculation of bile acids that led to a decrease in the plasma concentrations 
 of lipoproteins vldl and ldl , when compared to controls . lactobacillus supplementation also decreased fecal excretion of bile acids probably due to 
 their accumulation in lactobacillus probiotic cells . probiotic 
 administration also led to reductions of acetate in cecal content as well as of 
 the hepatic acetate to propionate ratio , which was related to a reduction in serum 
 lipids . furthermore , studies in vitro indicated that fecal commensal bacteria , but not probiotics , were 
 able to reduce cholesterol to coprostanol and thus increasing its excretion in 
 feces . some probiotic strains of the genus lactobacillus and bifidobacterium were also reported to synthesize conjugated 
 linolenic acid ( cla ) from polyunsaturated fatty acids of soy oil , which reduces 
 serum lipids and cholesterol in liver . one example of these bacteria is lactobacillus rhamnosus pl60 , which is a 
 human isolate that produces t10 , c12-conjugated linoleic acid and was found to exert 
 an antiobesity effect on diet - induced obese mice after 8 weeks of feeding . this 
 strain reduced body weight without reducing energy intake , and caused a 
 specific reduction of white adipose tissue without producing liver steatosis , 
 which is a common side effect of cla . obesity is considered an inflammatory disorder , 
 which affects both innate and adaptive immunity and favors the development of 
 other disorders such as type-2 diabetes and cardiovascular diseases . in 
 fact , chronic activation of innate immunity is regarded as a risk factor as it 
 favors the development of these disorders , which could also be influenced by the 
 gut microbiota [ 27 , 51 ] . the gut microbiota largely regulates innate and 
 adaptive immunity , influencing local and systemic responses ( figure 2 ) . the recognition of 
 bacterial components through pattern - recognition receptors ( prrs ) , such as toll - like 
 receptors ( tlrs ) of innate immune cells , is considered to be the starting point 
 of immunity , informing the immunocompetent cells to respond properly to each 
 environmental stimulus ( e.g. , pathogens or harmless microbes ) . tlr-4 
 recognizes lipopolysaccharide ( lps ) from gram - negative bacteria , while tlr-2 
 recognizes lipopeptides and lipoproteins from various pathogens , and 
 peptidoglycan and lipoteichoic acid from gram - positive bacteria ( figure 2 ) . 
 upon ligand binding , tlr interacts with different adaptor proteins ( myd88 , 
 tirap / mal , trif , and tram ) activating the transcription of different 
 downstream effector systems , such as the mitogen - activated kinases ( mapk ) , the 
 nf-b / ikk system , and the activator protein-1 ( ap-1 ) with 
 production of cytokines and diverse immune mediators . cytokines such as 
 tnf- , il-1 , and il-6 are the major proinflammatory 
 mediators produced in response to tlr-4 stimulation by endotoxin ( lps ) as well 
 as those increased in obese and insulin - resistant patients ( figure 2 ) . unlike 
 pathogenic microbes , commensal bacteria maintain a peaceful relationship with 
 their hosts by producing a transient activation of the nf-b cascade or its suppression by diverse 
 mechanisms including ( i ) promotion of nuclear export of nf-b subunit rela in complex with ppar- , ( ii ) inhibition of ib ubiquitination and degradation in epithelial 
 cells , ( iii ) regulation of tlr expression and upregulation of the negative 
 regulator tollip protein , and ( iv ) induction of anti - inflammatory cytokines such as il-10 . tlrs and derived cytokines also play a pivotal 
 role in linking innate and adaptive immunity through exerting action on t - cells 
 and particularly on dedritic cells ( dcs ) , keeping a physiological th1/th2 
 balance . th1-polarized responses characterized by overproduction of ifn- , il-2 , and il-12 cytokines are associated with 
 clearance of intracellular pathogens as well as with chronic diseases including 
 diabetes and obesity . most tlr - activated dcs induce differentiation of nave 
 cd4 + t cells into th1 cells , while tlr2-activated dcs promote the 
 differentiation of th2-cells or regulatory t cells by producing high levels of anti - inflammatory cytokine 
 il-10 which could help to counteract the inflammatory status associated with 
 obesity . interestingly , tlrs have been identified not only in innate and 
 adaptive immune cells but also in insulin - responsive tissues such as the adipose 
 tissue , muscle , and liver , suggesting a connection between immunity , microbial 
 stimulation , and metabolism . diet - induced and genetically obese mice ( ob / ob or db / db ) showed a 
 significant upregulation of expression of tlr-1 to -9 in adipocytes and 
 preadipocytes along with higher cytokine production upon stimulation . in particular , it is 
 known that tlr-4 can be activated 
 by both lipopolysaccharide ( lps ) and dietary - saturated fatty acids 
 inducing upregulation of common intracellular inflammatory pathways , 
 such as jnk and nf-b in adipocytes and macrophages , related to the 
 induction of insulin resistance and increased adiposity ( figure 2 ) . conversely , adipocyte - specific 
 knockdown of tlr4 prevented cytokine expression induced either by lps or 
 saturated fatty acids and similar effects were shown in macrophages . with some exceptions , loss - of - functional mutation in tlr-4 also prevented diet - induced obesity and 
 insulin resistance in vivo mice 
 models . recently , 
 metabolic endotoxaemia , characterized by an 
 increase in serum lps levels , has been demonstrated to be an inflammatory 
 factor , causative of body weight gain , insulin resistance , and diabetes in 
 high - fat fed animal models [ 27 , 61 ] . in contrast , the 
 inhibition of the gut microbiota by antibiotic administration ( norfloxacin and 
 ampicillin ) in two different mouse models of insulin resistance resulted in 
 reduced serum lps levels , low - grade inflammation , obesity , and type-2 diabetes , 
 demonstrating the link between the gut microbiota and certain metabolic 
 disorders . lps stimulation also produces a cytokine - mediated increase in 
 plasma lipid levels by increasing the synthesis of vldl lipoproteins in the 
 liver and inhibiting lipoprotein lipase . in fact , mobilization of lipid stores 
 is considered a mechanism to fuel the host 's response against infections ; 
 moreover , lipoproteins also seem to help fight against infection by binding and 
 neutralizing lps . pathogenic lipid nutrients  and microorganisms 
 mainly related to tlr-4-signaling and proinflammatory cytokine and gene 
 transcription activation pathways . in this scenario , one can hypothesize that shifts 
 in gut microbiota composition caused by a high - saturated fatty acid - containing 
 diet , 
 together with dietary lipids , 
 could constitute synergic tlr signals , thus contributing to the amplification 
 of inflammation occurring in obesity . consequently , it has been suggested that probiotics 
 and prebiotics with anti - inflammatory properties could be of help in the fight 
 against obesity and 
 associated disorders , as reported in other chronic inflammatory diseases . although few specific studies have proven such 
 a hypothesis so far , the administration of the probiotic vsl3 # was demonstrated 
 to exert a preventive effect against type-1 diabetes in a nonobese diabetic 
 mice model by immunomodulatory mechanisms , inducing il-10 production in peyer patches , 
 and spleen and its expression in the pancreas . in addition , lactobacillus culture - supernatants were 
 shown to reduce in vitro leptin 
 production by adipocytes , thereby reducing ifn- production by lymphocytes and exerting an 
 anti - inflammatory role . oral administration of a functional food product 
 containing l. plantarum 299v to heavy 
 smokers for six weeks led to a decrease in leptin , systolic blood pressure , and 
 fibrinogen , which was attributed to the anti - inflammatory effects of this 
 probiotic , suggesting it would be able to reduce cardiovascular risk . in 
 contrast , oral administration of lactobacillus 
 acidophilus and bifidobacterium 
 longum strains to human subjects did not influence serum leptin levels . the administration of a prebiotic ( oligofructose ) to high - fat - diet fed mice was 
 also shown to restore bifidobacterium levels , which positively correlated with improved glucose tolerance , 
 glucose - induced insulin secretion , and normalization of inflammatory tone by 
 decreasing endotoxaemia in plasma and proinflammatory cytokines in adipose 
 tissue . gut microbes are viewed as novel factors 
 involved in host physiology and body weight regulation by driving a number of 
 metabolic and immune functions . the initial association of the microbial 
 colonization process of the germ - free intestine with body weight gain conferred 
 a negative role to gut microbes with respect to obesity . further , relationships 
 established between a specific microbiota structure and a lean or obese 
 phenotype have suggested that different microbes may influence body weight 
 differently , and species- and stain - specific functions are being defined . in 
 addition , endotoxaemia and dysbiosis have been identified as inflammatory 
 factors responsible for insulin resistance and body weight , thereby returning 
 to the concept that a healthy microbiota may be beneficial in preventing these 
 disorders . although the cause - effect relationships of the gut microbiota with 
 obesity remain unclear and a limited number of in vivo trials have been done to assess the effects of specific 
 microbial strains ( commensals and probiotics ) , and prebiotics on metabolic 
 disorders , the knowledge provided by these studies constitutes a breakthrough 
 in the identification of their etiology . omic  technologies ( metagenomics , trancriptomics , and 
 metabolomics ) will be critical to shed light on the roles of specific sets of 
 microbes on metabolic disorders , with a view to 
 design more efficient 
 dietary - based strategies to reduce their risk .
obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence . 
 obesity results from an imbalance between energy intake and expenditure , associated with a chronic low - grade inflammation . 
 gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions . 
 the gut microbiota as a whole improves the host 's ability to extract and store energy from the diet leading to body weight gain , while specific commensal microbes seem to exert beneficial effects on bile salt , lipoprotein , and cholesterol metabolism . the gut microbiota and 
 some probiotics also regulate immune functions , protecting the host form infections and chronic inflammation . 
 in contrast , dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain . in the light of the link between the gut microbiota , metabolism , and immunity , 
 the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders . 
 although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders , the findings indicate that advances in this field could be of value in the struggle against obesity and its associated - metabolic disorders .