until recently , babies were believed to be born sterile and only populated by microbes on exposure to their first postdelivery environments ( 1 ) . however , the process of microbial colonization may begin before birth , with transfer between mother and baby taking place via the placenta ( 2 ) , and perhaps influenced by changes in the mother 's microbiome during pregnancy ( 3 , 4 ) . subsequently , the process of vaginal delivery allows for direct transfer of microbes from the birth canal and the perianal area to the baby ( 57 ) . finally , breastfeeding seems to provide and support specific microbes during the early phases of colonization within the infant gut ( 810 ) . throughout infancy and early childhood , there are changes in the gut composition that are related to microbial successions , whereby factors such as diet and host immune status appear to confer a  permanent resident status for some microbes but not others ( 8 , 1113 ) . this process of building a gut microbiota is still poorly understood , but it is believed to be of critical importance , because there is increasing evidence that a window of time exists for the gut microbiota to develop ( 13 ) . beginning at the time of weaning , the microbiota composition stabilizes and matures ( 12 , 14 ) ; from this point , it can be maintained with only minor changes over many months or years and perhaps even an entire lifetime ( 1518 ) . the gut microbiota represents one of the densest ecosystems on earth , and is composed not only of bacteria ( which are the most studied components of this niche ) but also of archaea , yeasts , protists , and viruses . around 5001,000 different bacterial species may be present in the gut of a given individual ( 19 , 20 ) , although at present the species concept in bacteria is imprecise ( because of the propensity for bacteria to share genetic information , for example ) ( 21 , 22 ) . the colon is the most densely populated compartment , with bacterial numbers reaching 1010 cells per gram of content ( 23 ) . the viral microbiome ( the  virome ) load is estimated to be higher than that of the bacterial load , with the majority being viruses that infect bacteria and archaea ( bacteriophage ) ( 24 , 25 ) . yeasts and other eukaryotes ( e.g. protists ) are estimated to make up only a small fraction of the colonic microbiota ( 26 , 27 ) . diet seems to be an important driver of microbial abundance profiles within an ecosystem ( 28 , 29 ) . given that most humans are omnivores with diverse diets , this is not surprising ; availability of a large selection of dietary substrates promotes the need for a large variety of metabolic pathways for processing , and it is the gut microbiota that takes on the lion 's share of this work for its host ( 30 ) . the resultant microbial diversity , and consequent functional redundancy within an ecosystem , supports overall ecosystem resilience and stability ( 31 , 32 ) . since resilience and stability largely define the ability of an ecosystem to resist stress , diversity is key to the overall health of the gut microbiota ( 33 ) . the functional redundancy of the gut microbiota can also be seen when looking at the human population as a group . there is much variation in the composition of the gut microbiome between individuals , due in large part to the multitude of environmental factors and host genetic influences that work in combination to build a microbiome ( 30 ) . however , the species variability that can be seen in the microbiomes of different people belies the fact that functionally these microbiomes can be quite similar ( 34 ) . even though the exact species content may differ widely , the composite genes of each microbiota as a whole can encode for a very similar group of proteins , or for proteins of similar functions . having established the importance of microbial community diversity , it is not surprising that a growing body of literature indicates that many chronic diseases are associated with less diverse gut ecosystems ( 35 , 36 ) . at the moment , this phenomenon is mainly associative , as it is difficult to ascertain whether reduced diversity occurs as a result of disease or vice versa . however , in some cases ( e.g. clostridium difficile infection , cdi ) , disease certainly results from a loss of gut microbiota diversity and robustness ( 36 ) . it is undoubtedly true ( both on the micro and macro scale ) that ecosystems which lack functional redundancy are more prone to collapse under perturbational stress . an imbalance within the microbial ecosystem (  dysbiosis ) of the human gut microbiota could result from many different scenarios ( fig . 2 ) , including : insufficient colonization of an infant ( e.g. due to caesarean section ) and/or inadequate nursing with breastmilk ; exposure to antibiotics , both as short - term therapy as well as long - term pervasive exposure through the food chain ; infection with pathogenic microbes ; and consumption of a refined , western - style diet with little fiber [ which is an important food source for colonic bacteria ( 29 , 3740 ) ] . recently , proponents of the  missing microbiota hypothesis have warned that modern lifestyles do not sustain a diverse human microbiome , and that the extinction of important keystone microbes could lead to the loss of fundamental functional abilities , which would ultimately contribute to dysbiosis and disease ( 41 ) . pictorial representation of the routes for , and blockages of , microbial colonization of westernized humans during early life . 
 on the left of the figure , routes of natural colonization are depicted , while on the right , impediments to natural colonization are shown . from a microbiological perspective , the loss of keystone species from the microbiome may impact the subsequent behavior of the remaining microbes . for example , when c. difficile is present as part of a diverse gut microbiota , it is unlikely to cause problems to the host because its overall abundance and pathogenic behavior are suppressed by the majority presence of the rest of the microbial species in the ecosystem ( 36 ) . however , loss of ecosystem diversity , usually brought about by antibiotic use , allows c. difficile to proliferate unchecked , and to upregulate virulence determinants that go on to cause disease ( 42 ) . in this way , c. difficile behaves somewhat like a hoodlum in a subway station ; when the subway station is crowded with people , the hoodlum is likely to behave appropriately , perceiving scrutiny by the crowd on the platform . but if the subway station is deserted , the hoodlum may start to vandalize the area , his / her behavior influenced by the lack of surveillance . the case of c. difficile illustrates the importance of the entire gut microbial ecosystem in disease , rather than individual species . traditional approaches to clinical microbiology have focused largely on the study and surveillance of specific pathogenic microbial species with well - defined virulence determinants , but our simple  one microbe - one disease models will have to change to incorporate a more complete understanding of microbiome dysbiosis in infection . one of the more startling revelations in the field of microbiology is that microbes are able to communicate with each other using chemical languages , with such communication is now known to govern a wide range of functions , including bacterial movement , gene expression , and community structure ( 44 , 45 ) . furthermore , these same signals may impact the host ; small molecules , by their nature , can readily pass through host cells and tissues , and may influence host gene expression and behavior as a result ( 46 , 47 ) . this process could , in fact , be to our evolutionary advantage , forging a beneficial connection between host and symbionts . laboratory mice that are reared under germ - free conditions can exhibit behavioral and gene expression patterns that differ from those that are raised in conventional conditions ( 48 , 49 ) . another striking example of the influence of the gut microbiota on behavior was demonstrated by bercik et al . , who showed that switching the gut microbiota of a timid mouse line ( c57bl/6 ) with that of a more aggressive mouse line ( nih swiss ) resulted in a concurrent switch in behavioral profiles ( 50 ) . bacterial colonization of the gut likely modulates host neural development through signaling pathways that include the use of the vagus nerve , a direct conduit between the gut and the central nervous system ( and hence the brain ) ( 51 ) . with the new realization of the influence of the gut microbiota on the brain , is it time that certain diseases traditionally thought to be brain disorders be considered as rooted in the gut microbiota ? incidence rates of asd in north america have risen rapidly in recent decades ( 52 , 53 ) , and although it is important to note that these figures have been influenced by changes in diagnostic practices , heightened public awareness , and varying research methodology , there remains a dramatic upward trend that can only be partly explained by these aforementioned factors . although asd is traditionally thought to have strong inheritance , single gene disorders and chromosomal abnormalities only account for a minority of asd cases ( 54 ) , and genome wide association studies have found hundreds of genetic variations to be potentially linked with asd ( 55 ) ; these observations argue against the prevailing view that the disorder is purely genetic in nature . many patients on the severe end of the autism spectrum present with gastrointestinal comorbidities that can include diarrhea , constipation , bloating , and abdominal pain ( 56 ) . the propensity for associated gi issues in many asd children has led some researchers to hypothesize a gut microbial involvement in disease . molecular profiling methods have been used to look for differences in the compositions of the gut microbiotas of asd and healthy individuals by examining stool samples , and different studies have yielded different results . found significant increases in clostridium bolteae and clostridium clusters i and xi ( 57 ) , finegold et al . noted an increase of desulfovibrio spp . ( 58 ) , and wang et al . observed higher levels of sutterella and ruminococcus spp . ( 59 ) in individuals with asd compared to controls . these may not be conflicting findings ; instead , these compositional changes could be indicative of gut dysbiosis in asd , and certainly there is potential here for the development of disease biomarkers . to date , no causative role has been suggested for these , or any other , individual microbial species , and indeed the functional complexity within the gut microbiota argues against a simple one microbe - one disease model . given the importance of the functionality of the microbiota over its precise composition , and also taking into account the importance of the gut microbiota in neural development and function , is it possible that a reduction in the gut microbiota diversity leads to a loss of key signals required for normal brain maturation ? this could possibly be triggered by the use of antibiotics in early childhood during the critical window for microbiota development , an event that is commonly ( if anecdotally ) cited by parents of children with asd ; indeed , several studies report increased use of oral antibiotics in children with asd compared to neurotypical children ( 6063 ) . if this is the case , the study of individual components of the gut microbiota will likely not be fruitful as the gut microbial ecosystem as a whole entity must be considered . this is currently limited by technical constraints that we and others are trying to address . advances in the ability to culture whole gut microbial ecosystems in vitro will allow a more holistic view of the structure of the gut microbiota , as well as its potential function in the context of asd . for example , continuous culture ( chemostat ) systems allow for the culture of whole , explanted , gut ecosystems under tightly controlled experimental conditions ( 64 ) , with the added advantage that small molecule metabolites produced by the resident ecosystem can be easily captured and characterized ( unpublished observations ) . is asd a gut - mediated disease ? clearly there is much work to be done to gain a fuller understanding of what is involved in the etiology of this complex disorder . as with other complex chronic diseases ( such as inflammatory bowel disease ) , ongoing research will likely draw us to the intersection between host genetics and epigenetics , microbiota structure and function , and environmental cues . however , this new and developing view of asd etiology presents an additional avenue for study . e.a - v is a cofounder of nubiyota llc , a company that is engaged in developing and commercializing therapeutic microbial ecosystems for medical use .
the human gut microbiota is a complex microbial ecosystem that contributes an important component towards the health of its host . 
 this highly complex ecosystem has been underestimated in its importance until recently , when a realization of the enormous scope of gut microbiota function has been ( and continues to be ) revealed . 
 one of the more striking of these discoveries is the finding that the gut microbiota and the brain are connected , and thus there is potential for the microbiota in the gut to influence behavior and mental health . in this short review , 
 we outline the link between brain and gut microbiota and urge the reader to consider the gut microbiota as an ecosystem  organ rather than just as a collection of microbes filling a niche , using the hypothesized role of the gut microbiota in autism spectrum disorder to illustrate the concept .