Microbial community in human gut: a therapeutic prospect and implication in health and diseases

The interest in the working and functionality of the human gut microbiome has increased drastically over the years. Though the existence of gut microbes has long been speculated for long over the last few decades, a lot of research has sprung up in studying and understanding the role of gut microbes in the human digestive tract. The microbes present in the gut are highly instrumental in maintaining the metabolism in the body. Further research is going on in this field to understand how gut microbes can be employed as potential sources of novel therapeutics; moreover, probiotics have also elucidated their significant place in this direction. As regards the clinical perspective, microbes can be engineered to afford defence mechanisms while interacting with foreign pathogenic bodies. More investigations in this field may assist us to evaluate and understand how these cells communicate with human cells and promote immune interactions. Here we elaborate on the possible implication of human gut microbiota into the immune system as well as explore the probiotics in the various human ailments. Comprehensive information on the human gut microbiome at the same platform may contribute effectively to our understanding of the human microbiome and possible mechanisms of associated human diseases.     

Gut microbiome composition and metabolomic profiles of wild western lowland gorillas (Gorilla gorilla gorilla) reflect host ecology

The metabolic activities of gut microbes significantly influence host physiology; thus, characterizing the forces that modulate this micro‐ecosystem is key to understanding mammalian biology and fitness. To investigate the gut microbiome of wild primates and determine how these microbial communities respond to the host's external environment, we characterized faecal bacterial communities and, for the first time, gut metabolomes of four wild lowland gorilla groups in the Dzanga‐Sangha Protected Areas, Central African Republic. Results show that geographical range may be an important modulator of the gut microbiomes and metabolomes of these gorilla groups. Distinctions seemed to relate to feeding behaviour, implying energy harvest through increased fruit consumption or fermentation of highly fibrous foods. These observations were supported by differential abundance of metabolites and bacterial taxa associated with the metabolism of cellulose, phenolics, organic acids, simple sugars, lipids and sterols between gorillas occupying different geographical ranges. Additionally, the gut microbiomes of a gorilla group under increased anthropogenic pressure could always be distinguished from that of all other groups. By characterizing the interplay between environment, behaviour, diet and symbiotic gut microbes, we present an alternative perspective on primate ecology and on the forces that shape the gut microbiomes of wild primates from an evolutionary context.     

Temporal variation selects for diet–microbe co-metabolic traits in the gut of Gorilla spp

Although the critical role that our gastrointestinal microbes play in host physiology is now well established, we know little about the factors that influenced the evolution of primate gut microbiomes. To further understand current gut microbiome configurations and diet–microbe co-metabolic fingerprints in primates, from an evolutionary perspective, we characterized fecal bacterial communities and metabolomic profiles in 228 fecal samples of lowland and mountain gorillas (G. g. gorilla and G. b. beringei, respectively), our closest evolutionary relatives after chimpanzees. Our results demonstrate that the gut microbiomes and metabolomes of these two species exhibit significantly different patterns. This is supported by increased abundance of metabolites and bacterial taxa associated with fiber metabolism in mountain gorillas, and enrichment of markers associated with simple sugar, lipid and sterol turnover in the lowland species. However, longitudinal sampling shows that both species'' microbiomes and metabolomes converge when hosts face similar dietary constraints, associated with low fruit availability in their habitats. By showing differences and convergence of diet–microbe co-metabolic fingerprints in two geographically isolated primate species, under specific dietary stimuli, we suggest that dietary constraints triggered during their adaptive radiation were potential factors behind the species-specific microbiome patterns observed in primates today.     

Gut microbes in cardiovascular diseases and their potential therapeutic applications

Microbial ecosystem comprises a complex community in which bacteria interact with each other.The potential roles of the intestinal microbiome play in human health have gained considerable attention.The imbalance of gut microbial community has been looked to multiple chronic diseases.Cardiovascular diseases(CVDs)are leading causes of morbidity worldwide and are influ-enced by genetic and environmental factors.Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome.in this review,we highlight the complex interplay between microbes,their metabolites,and the potential influence on the generation and development of CVDs.The therapeutic potentiai of using intestinal microbiomes to treat CVD is also discussed.it is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.     

Deep sequencing of the oral microbiome reveals signatures of periodontal disease

The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (~2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ~90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes.     

Convergent evolution of the gut microbiome in marine carnivores

The gut microbiome can help the host adapt to a variety of environments and is affected by many factors. Marine carnivores have unique habitats in extreme environments. The question of whether marine habitats surpass phylogeny to drive the convergent evolution of the gut microbiome in marine carnivores remains unanswered. In the present study, we compared the gut microbiomes of 16 species from different habitats. Principal component analysis (PCA) and principal coordinate analysis (PCoA) separated three groups according to their gut microbiomes: marine carnivores, terrestrial carnivores, and terrestrial herbivores. The alpha diversity and niche breadth of the gut microbiome of marine carnivores were lower than those of the gut microbiome of terrestrial carnivores and terrestrial herbivores. The gut microbiome of marine carnivores harbored many marine microbiotas, including those belonging to the phyla Planctomycetes, Cyanobacteria, and Proteobacteria, and the genus Peptoclostridium. Collectively, these results revealed that marine habitats drive the convergent evolution of the gut microbiome of marine carnivores. This study provides a new perspective on the adaptive evolution of marine carnivores.     

Small to modest impact of social group on the gut microbiome of wild Costa Rican capuchins in a seasonal forest

The horizontal transmission of pathogenic and beneficial microbes has implications for health and development of socially living animals. Social group is repeatedly implicated as an important predictor of gut microbiome structure among primates, with individuals in neighboring social groups exhibiting distinct microbiomes. Here we examine whether group membership is a predictor of gut microbiome structure and diversity across three groups of white‐faced capuchins (Cebus capucinus imitator) inhabiting a seasonal Costa Rican forest. We collected 62 fecal samples from 18 adult females during four sampling bouts. Sampling bouts spanned the dry‐to‐wet‐to‐dry seasonal transitions. To investigate gut microbial composition, we sequenced the V4 region of the 16S rRNA gene. We used the DADA2 pipeline to assign amplicon sequence variants and the RDP database to classify taxa. Our findings are: 1) gut microbiomes of capuchins clustered by social group in the late dry season, but this pattern was less evident in other sampling bouts; 2) social group was a significant variable in a PERMANOVA test of beta diversity, but it accounted for less variation than season; 3) social group was not an important predictor of abundance for the ten most abundant microbial taxa in capuchins; 4) when examining log2‐fold abundances of microbes between social groups, there were significant differences in some pairwise comparisons. While this is suggestive of group‐wide differences, individual variation may have a strong impact and should be assessed in future studies. Overall, we found a minor impact of social group membership on the gut microbiota of wild white‐faced capuchins. Future research including home range overlap and resource use, as well as fine‐scale investigation of individual variation, will further elucidate patterns of socially structured microbes.     

New challenges in the study of the evolution of wild animals and their gut microbiome

In this viewpoint, by reviewing the recent findings on wild animals and their gut microbiomes, we found some potential new insights and challenges in the study of the evolution of wild animals and their gut microbiome. We suggested that wild animal gut microbiomes may come from microbiomes in the animals'' living habitats along with animals'' special behavior, and that the study of long‐term changes in gut microbiomes should consider both habitat and special behaviors. Also, host behavior would facilitate the gut microbiome transmission between individuals. We suggested that research should integrate the evolutionary history and physiological systems of wild animals to understand the evolution of animals and their gut microbiomes. Finally, we proposed the Noncultured‐Cultured‐Fermentation‐Model Animal pipeline to determine the function (diet digestion, physiology, and behavior) of these target strains in the wild animal gut.     

Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes.

Numerous microbes inhabit the human intestine, many of which are uncharacterized or uncultivable. They form a complex microbial community that deeply affects human physiology. To identify the genomic features common to all human gut microbiomes as well as those variable among them, we performed a large-scale comparative metagenomic analysis of fecal samples from 13 healthy individuals of various ages, including unweaned infants. We found that, while the gut microbiota from unweaned infants were simple and showed a high inter-individual variation in taxonomic and gene composition, those from adults and weaned children were more complex but showed a high functional uniformity regardless of age or sex. In searching for the genes over-represented in gut microbiomes, we identified 237 gene families commonly enriched in adult-type and 136 families in infant-type microbiomes, with a small overlap. An analysis of their predicted functions revealed various strategies employed by each type of microbiota to adapt to its intestinal environment, suggesting that these gene sets encode the core functions of adult and infant-type gut microbiota. By analysing the orphan genes, 647 new gene families were identified to be exclusively present in human intestinal microbiomes. In addition, we discovered a conjugative transposon family explosively amplified in human gut microbiomes, which strongly suggests that the intestine is a 'hot spot' for horizontal gene transfer between microbes.     

Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities

Background

Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys.

Methodology/Principal Findings

We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny.

Conclusion/Significance

Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome.     

Mitochondria,the gut microbiome and ROS

In this review, we discuss the connections between mitochondria and the gut microbiome provided by reactive oxygen species (ROS). We examine the mitochondrion as an endosymbiotic organelle that is a hub for energy production, signaling, and cell homeostasis. Maintaining a diverse gut microbiome is generally associated with organismal fitness, intestinal health and resistance to environmental stress. In contrast, gut microbiome imbalance, termed dysbiosis, is linked to a reduction in organismal well-being. ROS are essential signaling molecules but can be damaging when present in excess. Increasing ROS levels have been shown to influence human health, homeostasis of gut cells, and the gastrointestinal microbial community's biodiversity. Reciprocally, gut microbes can affect ROS levels, mitochondrial homeostasis, and host health. We propose that mechanistic understanding of the suite of bi-directional interactions between mitochondria and the gut microbiome will facilitate innovative interdisciplinary studies examining evolutionary divergence and provide novel treatments and therapeutics for disease.GlossIn this review, we focus on the nexus between mitochondria and the gut microbiome provided by reactive oxygen species (ROS). Mitochondria are a cell organelle that is derived from an ancestral alpha-proteobacteria. They generate around 80% of the adenosine triphosphate that an organism needs to function and release a range of signaling molecules essential for cellular homeostasis. The gut microbiome is a suite of microorganisms that are commensal, symbiotic and pathogenic to their host. ROS are one predominant group of essential signaling molecules that can be harmful in excess. We suggest that the mitochondria- microbiome nexus is a frontier of research that has cross-disciplinary benefits in understanding genetic divergence and human well-being.     

Microbiomes in Canidae

Because of their range expansion across North America, coyotes (Canis latrans) now occur sympatrically with numerous other predator species, including red foxes (Vulpes vulpes). This raises several interesting ecological questions, including if and how sympatry affects the diet and gut microbiomes of coyotes and red foxes. We examined the gut microbiomes of sympatric populations of coyotes and red foxes within two different National Parks in Virginia, USA, that differ in land use, vegetation, and anthropogenic disturbance: Prince William Forest Park (PRWI) and Manassas National Battlefield Park (MANA). From 2012 to 2017, scat samples from PRWI and MANA were collected and analyzed. Polymerase chain reaction (PCR) amplification of a region of the mitochondrial cytochrome‐b gene followed by restriction enzyme digestion of the PCR product was used to determine the origin of each scat sample. Next‐Generation DNA sequencing of a hypervariable 16S rRNA gene region was used to determine gut microbiome information about the scat samples. There was no evidence for a difference between the gut microbiomes of red foxes in either location, or for a difference between the gut microbiomes of red foxes at either location and coyotes at the location with lower human disturbance, PRWI. However, the gut microbiomes of coyotes at the location with higher anthropogenic disturbances, MANA, revealed a marked change from those found in red foxes at either location and from those in coyotes at the location with lower disturbances. The gut microbiomes of coyotes subjected to greater human impact may provide evidence of dysbiosis, indicative of increased physiological stress and reduced health. We discuss our observations in the context of understanding anthropogenic impacts on coyote and red fox interactions. Our results suggest that physiological stress in the form of human disturbance may play an important role in the composition of the gut microbiome of coyotes, which can affect their overall health.     

Progressive deterioration of the upper respiratory tract and the gut microbiomes in children during the early infection stages of COVID-19

Children are less susceptible to coronavirus disease 2019 (COVID-19), and they have manifested lower morbidity and mortality after infection, for which a multitude of mechanisms may be considered. Whether the normal development of the gut-airway microbiome in children is affected by COVID-19 has not been evaluated. Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection alters the upper respiratory tract and the gut microbiomes in nine children. The alteration of the microbiome is dominated by the genus Pseudomonas, and it sustains for up to 25e58 days in different individuals. Moreover, the patterns of alternation are different between the upper respiratory tract and the gut. Longitudinal investigation shows that the upper respiratory tract and the gut microbiomes are extremely variable among children during the course of COVID-19. The dysbiosis of microbiome persists in7 of 8 children for at least 19e24 days after discharge from the hospital. Disturbed development of both the gut and the upper respiratory microbiomes and prolonged dysbiosis in these nine children imply possible long-term complications after clinical recovery from COVID-19, such as predisposition to the increased health risk in the post-COVID-19 era.     

Social convergence of gut microbiomes in vampire bats

The ‘social microbiome’ can fundamentally shape the costs and benefits of group-living, but understanding social transmission of microbes in free-living animals is challenging due to confounding effects of kinship and shared environments (e.g. highly associated individuals often share the same spaces, food and water). Here, we report evidence for convergence towards a social microbiome among introduced common vampire bats, Desmodus rotundus, a highly social species in which adults feed only on blood, and engage in both mouth-to-body allogrooming and mouth-to-mouth regurgitated food sharing. Shotgun sequencing of samples from six zoos in the USA, 15 wild-caught bats from a colony in Belize and 31 bats from three colonies in Panama showed that faecal microbiomes were more similar within colonies than between colonies. To assess microbial transmission, we created an experimentally merged group of the Panama bats from the three distant sites by housing these bats together for four months. In this merged colony, we found evidence that dyadic gut microbiome similarity increased with both clustering and oral contact, leading to microbiome convergence among introduced bats. Our findings demonstrate that social interactions shape microbiome similarity even when controlling for past social history, kinship, environment and diet.     

Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes

The gastrointestinal (GI) microbiome contributes significantly to host nutrition and health. However, relationships involving GI microbes, their hosts and host macrohabitats remain to be established. Here, we define clear patterns of variation in the GI microbiomes of six groups of Mexican black howler monkeys (Alouatta pigra) occupying a gradation of habitats including a continuous evergreen rainforest, an evergreen rainforest fragment, a continuous semi-deciduous forest and captivity. High throughput microbial 16S ribosomal RNA gene sequencing indicated that diversity, richness and composition of howler GI microbiomes varied with host habitat in relation to diet. Howlers occupying suboptimal habitats consumed less diverse diets and correspondingly had less diverse gut microbiomes. Quantitative real-time PCR also revealed a reduction in the number of genes related to butyrate production and hydrogen metabolism in the microbiomes of howlers occupying suboptimal habitats, which may impact host health.     

Primate microbiomes over time: Longitudinal answers to standing questions in microbiome research

To date, most insights into the processes shaping vertebrate gut microbiomes have emerged from studies with cross‐sectional designs. While this approach has been valuable, emerging time series analyses on vertebrate gut microbiomes show that gut microbial composition can change rapidly from 1 day to the next, with consequences for host physical functioning, health, and fitness. Hence, the next frontier of microbiome research will require longitudinal perspectives. Here we argue that primatologists, with their traditional focus on tracking the lives of individual animals and familiarity with longitudinal fecal sampling, are well positioned to conduct research at the forefront of gut microbiome dynamics. We begin by reviewing some of the most important ecological processes governing microbiome change over time, and briefly summarizing statistical challenges and approaches to microbiome time series analysis. We then introduce five questions of general interest to microbiome science where we think field‐based primate studies are especially well positioned to fill major gaps: (a) Do early life events shape gut microbiome composition in adulthood? (b) Do shifting social landscapes cause gut microbial change? (c) Are gut microbiome phenotypes heritable across variable environments? (d) Does the gut microbiome show signs of host aging? And (e) do gut microbiome composition and dynamics predict host health and fitness? For all of these questions, we highlight areas where primatologists are uniquely positioned to make substantial contributions. We review preliminary evidence, discuss possible study designs, and suggest future directions.     

Metabolically similar cohorts of bacteria exhibit strong cooccurrence patterns with diet items and eukaryotic microbes in lizard guts

Gut microbiomes perform essential services for their hosts, including helping them to digest food and manage pathogens and parasites. Performing these services requires a diverse and constantly changing set of metabolic functions from the bacteria in the microbiome. The metabolic repertoire of the microbiome is ultimately dependent on the outcomes of the ecological interactions of its member microbes, as these interactions in part determine the taxonomic composition of the microbiome. The ecological processes that underpin the microbiome's ability to handle a variety of metabolic challenges might involve rapid turnover of the gut microbiome in response to new metabolic challenges, or it might entail maintaining sufficient diversity in the microbiome that any new metabolic demands can be met from an existing set of bacteria. To differentiate between these scenarios, we examine the gut bacteria and resident eukaryotes of two generalist‐insectivore lizards, while simultaneously identifying the arthropod prey each lizard was digesting at the time of sampling. We find that the cohorts of bacteria that occur significantly more or less often than expected with arthropod diet items or eukaryotes include bacterial species that are highly similar to each other metabolically. This pattern in the bacterial microbiome could represent an early step in the taxonomic shifts in bacterial microbiome that occur when host lineages change their diet niche over evolutionary timescales.     

Analysis of Stomach and Gut Microbiomes of the Eastern Oyster (Crassostrea virginica) from Coastal Louisiana,USA

We used high throughput pyrosequencing to characterize stomach and gut content microbiomes of Crassostrea virginica, the Easter oyster, obtained from two sites, one in Barataria Bay (Hackberry Bay) and the other in Terrebonne Bay (Lake Caillou), Louisiana, USA. Stomach microbiomes in oysters from Hackberry Bay were overwhelmingly dominated by Mollicutes most closely related to Mycoplasma; a more rich community dominated by Planctomyctes occurred in Lake Caillou oyster stomachs. Gut communities for oysters from both sites differed from stomach communities, and harbored a relatively diverse assemblage of phylotypes. Phylotypes most closely related to Shewanella and a Chloroflexi strain dominated the Lake Caillou and Hackberry Bay gut microbiota, respectively. While many members of the stomach and gut microbiomes appeared to be transients or opportunists, a putative core microbiome was identified based on phylotypes that occurred in all stomach or gut samples only. The putative core stomach microbiome comprised 5 OTUs in 3 phyla, while the putative core gut microbiome contained 44 OTUs in 12 phyla. These results collectively revealed novel microbial communities within the oyster digestive system, the functions of the oyster microbiome are largely unknown. A comparison of microbiomes from Louisiana oysters with bacterial communities reported for other marine invertebrates and fish indicated that molluscan microbiomes were more similar to each other than to microbiomes of polychaetes, decapods and fish.     

Phylotyping and Functional Analysis of Two Ancient Human Microbiomes

Background

The Human Microbiome Project (HMP) is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas.

Methodology/Principal Findings

We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases.

Conclusions/Significance

We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today.