The Gut Microbiota in Mammals - Term Paper Example

?GUT MICROBIOTA IN MAMMALS I. Introduction: Gut of a mammal primarily comprises of esophagus, stomach, small intestine, large intestine and some of the accessory organs integral to the digestive function of gut; namely liver, pancreas and gall bladder (figure 1). The gut wall is four layered with a central lumen, lined by a mucous membrane or mucosa; next is the layer of connective tissues; followed by smooth muscles and finally the second layer of connective tissue (Karasov and Carey, 363) (figure 2). The gut is responsible for the twin functions of digestion as well as maintenance of immune homeostasis of the body. The anatomy of the gut is designed to perform efficiently both of these functions. To enable nutrient uptake, many associated digestive glands and multiple folding of the inner lining ensure thorough digestion and rapid assimilation of the nutrients. The gut associated lymphoid tissue on the other hand ensures that the internal environment of gut remains devoid of harmful foreign antigens. Besides these an important component of the gut is the gut microbiota, which together with the host form a composite body. So intimately is the existence of the two entwined, that the microbial community is collectively considered an organ of the host body; and the mammalian genome is referred to as metagenome, i.e. host genome along with the genome of its microbial community (Ley et al., 1647). The number and diversity of microbes residing indigenously in the gut environment is massive comprising of bacteria, protozoans, anaerobic phycomycetes and bacteriophages. Not only are they an integral part of the gut ecosystem, but they also contribute indispensably to the nutritional, physiological and immunological functions of the gut (Mackie, 13). Though the exact composition of the gut microbiota of different animals cannot be listed with certainty, yet the variations observed are primarily due to the differences in the diet of different animals. In animals with a particular diet, the environment within the gut is more or less constant and hence the microbial population is similar (Karasov and Carey, 363). Animals can be broadly classified in to three groups on the basis of their diet viz carnivores, omnivores and herbivores. In correlation with this, a study of gut microbiology would proceed in three parallel lines, for three classes of microbial consortia; one for each of these gut environments. This paper aims to discuss the functional significance of the microbial population in the gut of herbivores, omnivores and carnivores. Figure 1 Mammalian Gut Figure 2: Mammalian Gut Lining II. Role of Gut Microbiota in Herbivores: Herbivores derive their nutrition from plant components; hence it is imperative to possess the ability to digest plant cell wall. However, the cellulose component of plant cell wall makes it difficult to disintegrate. Herbivores therefore, during the course of evolution have acquired adaptations that enable them to disintegrate and assimilate this otherwise indigestible material (Karasov and Carey, 364). The herbivore mammalian foregut or hindgut is divided into chambers where fermentation of the food intake is carried out with help of microbial inhabitants of the gut. These chambers are known as rumen and the animals as ruminants. Due to exclusively plant based diet of herbivore, the role of gut microbe in herbivore gut assumes immense significance, the gut microbiota being imperative for digestion process in herbivores. This justifies an exclusive discussion of ruminant gut microbiota. Evolution of gut microbiota: Evolution of the digestive system of mammals to enable utilization of complex plant material proceeds parallel with the evolution of their gut microbiota. The ubiquitous microbes on one hand were easily able to colonize the mammals in general, but further evolutionary pattern was dependent on the diet of the host they inhabited. Thus the microbial population of the mammalian host coevolved with the evolving host digestive system. In herbivores as the gut became longer and developed compartments or rumen, either in the foregut or hindgut to accommodate the microbial fermentation of complex plant matter; the microbes too diversified with this complex diet pattern of their hosts (Ley, 1648). However the 16sRNA sequencing of the carnivore, omnivore and herbivore gut microbiota clearly indicates that the herbivore microbiota have not evolved from that of carnivore, but have been acquired independently. Moreover gut microbiota of herbivore Panda is found to be distinct from other animals of its group, which are carnivores, and similar to the herbivores in general. This indicates a convergent pattern of evolution of gut microbes, with the development of herbivory in animals of different classes (Ley 1650). The gut structures of mammalian herbivores exhibit some structural variations and hence the gut microbiota are exposed to varied environmental situations. While in ruminants like cows, deer, sloths, macropod marsupials etc; the fermentation procedure begins in the foregut, microbes getting to the food first. There is another group of herbivore where fermentation chamber lies closer to hindgut. In these animals the microbial community is able to feed on the remnants from the foregut, which is rich in cellulosic materials and low in other nutrients, since they have already been assimilated in small intestine (Gulati, 281). Role of Microbes in ruminants: The gut microbiota form a complex group with 104 to 1010 organisms of hundreds of species interacting intimately among themselves and with the host system. Most of these microbes are bacteria which contribute significantly to the nutrition of ruminants. The common rumen bacteria are Bacteroides ruminicola, Ruminobacter, Fibrobacter Oscillospira guillermondii, Lampropedia, Sarcina bakeri, Magnoovun eadii, large selenomonas, rosettes some cellulolytic cocci e.g. Ruminococcus and also Fibrobacter (Stewart and Bryant, 21). These microorganisms are responsible for degradation of ingested food which is fermented and assimilated. The chief substrate of rumen microbial population is carbohydrate, each molecule being metabolized to produce almost 4ATPs and short chain fatty acids (SCFAs) such as pyruvate or other metabolites (Hungate et al., 1105). The pyruvate is then further metabolized to other products. The utilization of cellulose and its fermentation products is similar in all classes of microbes, namely acetate, butyrate, lactate along with CO2 and H2. The hydrogen is immediately converted to methane and thus the partial pressure of H2 is maintained. The assimilation of these products occurs differently in these organisms. The cell components of protozoan being distinct from the rest, it definitely is expected to supply unique nutrients to host upon digestion finally by the host. These components such as essential amino acids, unsaturated fatty acids and vitamins have high nutritional value and therefore are of much significance to the host. The fungal population of the gut has the ability to degrade lignocelluloses and many other polysaccharide of cell wall such as xyaln, pullulan, pustulan, inulin and starch, the exceptions being pectin and polygalacturonate. The enzymes required for these degradations are produced by the fungi themselves and are all usually extracellular (Williams and Orpin, 1987). Some fungi such as Neocallimastix frontalis also produce metalloproteases and thus exhibit proteolytic activity. Besides this the fungal population of rumen influences the choline degradation and prevents the hydrogenation of essential fatty acids such as linolenic and linoleic acids in the rumen (Gulati et al., 1984). The ATP produced during the fermentation process is utilized by the microbes for protein synthesis using small nitrogenous molecules from the gut. While bacteria may utilize ammonia, protozoans are capable of using amino acids. Thus due to microbial population ruminants are able to convert non protein nitrogen to proteins. Some bacteria produce fatty acids and some specifically long chain fatty acids which are essential for and therefore, utilized by the host. Gut microbiota play important role in regulation of fat storage by the host system. They enable utilization of indigestible dietary fiber for energy extraction and thus add to the body fat more than what would be possible for a germ free individual being fed the same diet. The mechanism involves higher uptake of glucose in host intestine leading to elevated levels of serum glucose and insulin. This triggers a chain of events culminating in higher hepatic lipogenesis through effect on two transcription factors ChREBP and SREBP-1c (helix loop helix/ leucine zipper TF) (Bakhed et al., 1918). It has also been found that SCFAs (C1-C6) act as signaling molecules and are ligands binding to at least two G protein coupled receptors (Gpr41 and Gpr43). Thus these acids stimulate leptin, a hormone with pleiotropic effect on the appetite and energy metabolism (Samuel et al., 16767). As a consequence of these events elevated levels of triglycerides are introduced in the host circulation by liver and the same is imported by the adipocytes. The gut microbiota also suppress the LPL inhibitor thus overall effect being higher level of energy extraction and storage in form of adipose tissues (Bakhed et al., 1919). An abnormal microbial activity along with an unbalanced diet can therefore, lead to obesity. Gut microbes also help in production of vitamins using the 2-methyl-D-erythritol 4-phosphate pathway. Bacteria are responsible for the synthesis of vitamin K, Vitamin C, niacin, pantothenic acid, biotin, vitamin B12 and folic acid in the host gut. Bacterial and host interactions play a key role in maintenance of calcium levels of the host by inducing synthesis of vitamin D receptors by SCFAs produced by gut microbes. These short chain fatty acids also regulate calcium transport across epithelial cells and their storage within the cells through MAPK and PKC mediated signaling pathway. The store houses of calcium being bone and teeth in mammalian body; the overall effect of this is stronger bone and teeth (Resta, 4172). The fermentation products or products of other metabolic activities of herbivore gut microbiota are then available for the host metabolism. Finally the protein rich microbes migrate from the rumen to the intestine and are digested there. Thus the ruminants and their indigenous microbial population share a symbiotic relationship with each other (Kovatcheva-Datchary et al., S10). Besides this the rumen microbiota also play significant roles in the detoxification of some compounds ingested along with food. The protozoans have many hydrolytic and reducing enzymes which enable conversion of toxic compounds to non toxic products. For e.g. nitro groups of chloramphenicol, nitrophenols etc are reduced to amines through hydroxylamine intermediates. Aromatic nitro group of parathions on the other hand is converted by to aminoparathion, which is less toxic and is eliminated from host system. These protozoans are also able to reduce the toxicity due to copper, by degradation of insoluble proteins and thus making available higher concentration of pepetides and amino acids. These are consequently digested by bacteria formin sulphides that bind with Cu to form insoluble sulphides, which are excreted from the host system. Simiarly gut microbe Synergistes jonesii degrades mimosine, a toxic amino acid present in tropical legume Leucaena leucocephala, thus protecting the Hawaiian goat from their toxic effects (Karasov and Carey, 327). Role of microbes in non ruminants: Non ruminants like hippopotamus, kangaroo, elephants and hindgut fermenters such as rabbit, rodents, horse and pigs etc have a lesser dependence on their microbial population for derivation of nutritional benefits. Yet there are several advantages that can be attributed to their microbial inhabitants. Microbial fermentations in the hindgut produce products such as short chain fatty acids (SCFAs), lactate, ethanol etc, which are utilized by the host tissue for energy production. Besides this the gut microbiota, as in ruminants contributes to the protein and vitamin pool of the host system. Corpophagus non rumiants like rats reingest feces and along with it obtain amino acids such as lysine which are formed from urea by the microbiota inhabiting their cecum and colon. They also manage to introduce the hindgut microbiota back in to their digestive system by their corpophagy (Karasov and Carey, 327). Undigested nitrogenous material which enters the hindgut undergoes bacterial fermentation. The amino acids thus are decarboxylated to form amines. Most of these amines are toxic (e.g. cadaverine, tyramine etc), but some have pharmacological significance. E.g. histamine has high vasopressor activity, polyamines namely cadaverine, spermidine etc enhance cell division, tissue growth and also protein synthesis. Putrescine has been found to be useful in the prevention and recovery from the coccidosis because of its positive effect on intestine epithelium growth (Girdhar et al., 2006). Role of microbes in carnivore gut: Carnivore gut anatomy is simpler to that of herbivore and omnivore; designed to digest simple tissues of the other animals they feed on rather than the complex plant cells. They also need to consume less since their diet is energy rich. Hence they have simple stomachs with a short intestine, and cecum if present is much smaller in size compared to other categories of animals. In accordance the microbiota of the carnivore gut is not as diverse as that of omnivore. While the Bacteroides are lacking, the Fermicutes too are more like the free living communities rather than those found in omnivore and herbivore gut (Ley et al., 783). A 16S rRNA sequencing analysis of the microbes in the fecal matter of Polar bears of Arctic marine ecosystem revealed that all the sequences exhibit a similarity with the phylum Firmicutes, of which 99% are of the order Clostridiales. Approximately 70% of these belong to the genera Clostridium, with the most abundant being C. perfringens and next in order of abundance being C. bartletti (Glad et al., 10). However, not much information is available on the role of microbiota in the gut of carnivore. Role of microbes in omnivore gut: The finest example and the most cooperating subject for the study of omnivore characteristics is man. Human beings host trillions of microbes in their distal gut i.e. colon, performing essential metabolic functions which not only contribute to their physiology but are also significant and sometimes imperative for human physiology. They extract nutrients from the human diet and are important for the health of the host. Like other animals, omnivore gut too has a higher proportion of bacteria, up to 90% of which are Bacteriodes and Firmicutes. The combined genome content of gut microbes exceeds that of any omnivore (Ley, et al., 1368). The most important function of microbiota in the gut is its performance as a singular ‘organ’ capable of performing metabolic activities not yet evolved in the omnivore system. The primary diet substrates for colonic microbiota are polysaccharides such as starches and some proteins. The degradation of starches by saccharolytic bacteria in colon leads to formation of SCFAs which reduce pH and encourage growth of beneficial bacteria such as bifidobacteria and lactobacilli. Besides, studies have indicated the significance of butyrate and other SCFAs in prevention of colon cancer by encouraging growth of colon epithelial lining (Kovatcheva-Datchary et al., S9). Obesity induced by microbial activity has been implicated in release of various cytokines namely IL-1, TNF-?, and IL-6; which are inflammatory factors. These cytokines are also responsible for impaired insulin activity and lead to insulin resistance. Though the exact mechanism of these responses is not yet known, but lipopolysaccharide (LPS) component of gram negative bacteria is being speculated to be a probable candidate for inducing the synthesis of these cytokines and thus leading to type-2 diabetes in individuals on high fat diet. The dependence of host on its gut microbiota for its energy extraction efficiency from polysaccharide diet can be used for therapeutic purposes. Bacteroides thetaiotamicron is one of the inhabitants of distal gut omnivores which deserve a mention for its highly adaptive nutrient status. It is a glycophile with high ability to digest indigestible polysaccharides both from host dietary intake as well as host tissues when dietary intake is insufficient. It has the capacity to modulate its genome in accordance with the physiological functions required to be conducted depending on the gut environment (Zoetendal et al., 1645). Some more important microbial species of mammalian gut, with their specific roles are listed in table 1. Table 1: Impact of microbes on host response (Zoetendal et al., 1645) The gut micobiota in both ruminants and non ruminants prevents infections by pathogenic microbes (Xuesong et al., 665). The high density of well established microbiota, with their own niches in the gut ecosystem provides an intense competition to newly introduced infecting species which are also well outnumbered by the indigenous microbes. This is known as Nurmi concept, which describes the multifactorial phenomenon of microbial interference or competitive exclusion. Another important function of gut microbiota in general, can be attributed to the methanogens and acetogenic bacteria, which prevent the buildup of hydrogen in the gut by converting hydrogen to methane (figure 3). This results in higher metabolism of complex carbohydtrates and therefore higher energy extraction efficiency by other microbes of the gut microbial community (Karasov and Carey, 325). Figure 3: Pathways for the anaerobic degradation of food by gut microbiota (green arrow), red and blue arrows indicate alternative pathways for hydrogen utilization by Acetogens and Methanogens (Karasov and Carey, 325) Conclusion: Gut microbiota have been identified to play significant role in maintaining the health and nutritional supply of their host and have coevolved with host diet pattern. Though the exact components of microbial community in the gut is not yet known, nor the mechanisms by which these effects are brought about are fully understood, yet there is no denying the fact that gut microbiota are an integral component of host physiology. Manipulations of their characteristics and composition can enable us to exploit these microbes and derive benefits from their unique abilities. Further research is needed therefore, to understand and utilize these integral components of mammalian system. Work Cited 1. Bakhed, F. et al. "Host bacterial mutualism in humans." 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