Microbiota Genome Research Articles

Gut microbiota genome features associated with brain injury in extremely premature infants

ABSTRACT Severe brain damage is common among premature infants, and the gut microbiota has been implicated in its pathology. Although the order of colonizing bacteria is well described, the mechanisms underlying aberrant assembly of the gut microbiota remain elusive. Here, we employed long-read nanopore sequencing to assess abundances of microbial species and their functional genomic potential in stool samples from a cohort of 30 extremely premature infants. We identify several key microbial traits significantly associated with severe brain damage, such as the genomic potential for nitrate respiration and iron scavenging. Members of the Enterobacteriaceae were prevalent across the cohort and displayed a versatile metabolic potential, including pathogenic and nonpathogenic traits. Predominance of Enterobacter hormaechei and Klebsiella pneumoniae were associated with an overall loss of genomic functional redundancy as well as poor neurophysiological outcome. These findings reveal microbial traits that may be involved in exacerbating brain injury in extremely premature infants and provide suitable targets for therapeutic interventions.

Deciphering the Diversity in Bacterial Transporters That Salvage Queuosine Precursors.

Queuosine (Q) is a modification of the wobble base of tRNA harboring GUN anticodons with roles in decoding accuracy and efficiency. Its synthesis is complex with multiple enzymatic steps, and several pathway intermediates can be salvaged. The only two transporter families known to salvage Q precursors are QPTR/COG1738 and QrtT/QueT. Analyses of the distribution of known Q synthesis and salvage genes in human gut and oral microbiota genomes have suggested that more transporter families remain to be found and that Q precursor exchanges must occur within the structured microenvironments of the mammalian host. Using physical clustering and fusion-based association with Q salvage genes, candidate genes for missing transporters were identified and five were tested experimentally by complementation assays in Escherichia coli. Three genes encoding transporters from three different Pfam families, a ureide permease (PF07168) from Acidobacteriota bacterium, a hemolysin III family protein (PF03006) from Bifidobacterium breve, and a Major Facilitator Superfamily protein (PF07690) from Bartonella henselae, were found to allow the transport of both preQ0 and preQ1 in this heterologous system. This work suggests that many transporter families can evolve to transport Q precursors, reinforcing the concept of transporter plasticity.

Dissecting the HGT network of carbon metabolic genes in soil-borne microbiota.

The microbiota inhabiting soil plays a significant role in essential life-supporting element cycles. Here, we investigated the occurrence of horizontal gene transfer (HGT) and established the HGT network of carbon metabolic genes in 764 soil-borne microbiota genomes. Our study sheds light on the crucial role of HGT components in microbiological diversification that could have far-reaching implications in understanding how these microbial communities adapt to changing environments, ultimately impacting agricultural practices. In the overall HGT network of carbon metabolic genes in soil-borne microbiota, a total of 6,770 nodes and 3,812 edges are present. Among these nodes, phyla Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes are predominant. Regarding specific classes, Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacteroidia, Actinomycetia, Betaproteobacteria, and Clostridia are dominant. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional assignments of glycosyltransferase (18.5%), glycolysis/gluconeogenesis (8.8%), carbohydrate-related transporter (7.9%), fatty acid biosynthesis (6.5%), benzoate degradation (3.1%) and butanoate metabolism (3.0%) are primarily identified. Glycosyltransferase involved in cell wall biosynthesis, glycosylation, and primary/secondary metabolism (with 363 HGT entries), ranks first overwhelmingly in the list of most frequently identified carbon metabolic HGT enzymes, followed by pimeloyl-ACP methyl ester carboxylesterase, alcohol dehydrogenase, and 3-oxoacyl-ACP reductase. Such HGT events mainly occur in the peripheral functions of the carbon metabolic pathway instead of the core section. The inter-microbe HGT genetic traits in soil-borne microbiota genetic sequences that we recognized, as well as their involvement in the metabolism and regulation processes of carbon organic, suggest a pervasive and substantial effect of HGT on the evolution of microbes.

Assembly and analytical validation of a metagenomic reference catalog of human gut microbiota based on co-barcoding sequencing.

Human gut microbiota is associated with human health and disease, and is known to have the second-largest genome in the human body. The microbiota genome is important for their functions and metabolites; however, accurate genomic access to the microbiota of the human gut is hindered due to the difficulty of cultivating and the shortcomings of sequencing technology. Therefore, we applied the stLFR library construction method to assemble the microbiota genomes and demonstrated that assembly property outperformed standard metagenome sequencing. Using the assembled genomes as references, SNP, INDEL, and HGT gene analyses were performed. The results demonstrated significant differences in the number of SNPs and INDELs among different individuals. The individual displayed a unique species variation spectrum, and the similarity of strains within individuals decreased over time. In addition, the coverage depth analysis of the stLFR method shows that a sequencing depth of 60X is sufficient for SNP calling. HGT analysis revealed that the genes involved in replication, recombination and repair, mobilome prophages, and transposons were the most transferred genes among different bacterial species in individuals. A preliminary framework for human gut microbiome studies was established using the stLFR library construction method.

Plant microbiota dysbiosis and the Anna Karenina Principle.

Microorganisms are associated with all plants, recently leading to the hologenome concept. We reviewed the assembly processes of plant microbiota and analyzed its structure during the emergence of dysbioses. In particular, we discussed the Anna Karenina Principle (AKP) based on Leo Tolstoy's assertion applied to plant microbiota: 'All healthy microbiota are alike; each disease-associated microbiota is sick in its own way.' We propose the AKP to explain how stochastic processes in plant microbiota assembly due to several external stressors could lead to plant diseases. Finally, we propose the AKP to conceptualize plant dysbioses as a transitory loss of host capacity to regulate its microbiota, implying a loss of function that leads to a reduction of the host's fitness.

THE IMPACTS OF HEAVY METALS ON THE GUT MICROBIOME IN COMMON CARP (CYPRINUS CARPIO)

Pollution of freshwaters with heavy metals has become an acute problem in many countries including Kazakhstan, and industrial progress is the primary source of toxic heavy metals. Since gut microbe communities play a significant role in fishes’ homeostasis, immune regulation, metabolism, and disease resistance, it is crucial to understand how heavy metals affect fish's gastrointestinal microbiome diversity. Applications of metagenomics using the 16S rDNA gene's hypervariable regions allow researchers to sequence the gastrointestinal microbiota's genome and identify the diversity of microorganisms, including those that cannot be cultured with traditional microbiological methods. Common carp (Cyprinus carpio) is resistant to highly polluted freshwaters with heavy metals and considered a bioindicator of freshwater pollution. Thus, this paper aims to overview heavy metals' influence on the gastrointestinal microbiome diversity in common carp. Future directions are also discussed to enhance our understanding about the relationships between different environmental factors and gut microbiome diversity of wild fish. Further, it is crucial to understand how each bacterium would help common carp resist heavy metal toxicity.

Characterization of the Microbial Communities along the Gastrointestinal Tract in Crossbred Cattle.

Simple SummaryCrossbreeding has been used worldwide to improve milk production, milk composition, and reproduction performance. Understanding the structure of the microbial communities in the gastrointestinal tract (GIT) of crossbred cattle is paramount for developing new livestock management technologies with an emphasis on nutrition and sustainability. In this study, we investigated the gastrointestinal microbiota of Simmental × Holstein crossbred cattle using 16s rRNA gene sequencing. Microbial communities in the small intestine had the lowest diversity of bacteria and highest diversity of bacterial functions, and three groups of GIT regions, including the stomach, small intestine, and large intestine were characterized by specific bacteria and bacterial functions. In summary, spatial heterogeneity of the microbiota was found across the GIT of crossbreeds, and specific microbial biomarkers were identified in different regions.The gastrointestinal microbiota greatly affects the health status and production performance of bovines. Presently, many studies have used high-throughput sequencing methods to investigate the gastrointestinal microbiome in bovines. However, the microbiome profile of crossbred cattle across the whole gastrointestinal tract (GIT) has not been thoroughly reported. In this study, the digesta at ten regions (including the rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, colon, and rectum) of the GIT were collected in three Simmental × Holstein crossbred heifers aged 17 months, and microbial DNA was extracted and amplified for sequencing of the V3–V4 regions of the 16S rRNA gene. Functional orthologs of the microbiota genome were predicted and analyzed. We found that samples were categorized into three groups (the stomach, small intestine, and large intestine) by principal coordinate analysis (PCoA) based on Bray–Curtis dissimilarity in both the bacterial composition and functional profile. Samples from small intestine had the lowest alpha diversity of bacteria composition and highest alpha diversity of the functional composition. Three groups of GIT regions were characterized by several microbiome features. The stomach was characterized by Bacteroidetes and Fibrobacteres at the phylum level, and KEGG pathways related to the metabolism of cofactors and vitamins, glycan biosynthesis, and metabolism were enriched in the stomach. The small intestine was characterized by Actinobacteria and Patescibacteria at the phylum level, and KEGG pathways related to xenobiotics biodegradation and metabolism were enriched in the small intestine. The large intestine featured Ruminococcaceae, Rikenellaceae, and Bacteroidacea at the family level, and KEGG pathways, including steroid hormone biosynthesis, linoleic acid metabolism, and cysteine and methionine metabolism were enriched in the large intestine. The results of the current study revealed the spatial heterogeneity of microbiota across the GIT in Simmental × Holstein crossbreeds and identified microbial biomarkers of different regions. The results can provide useful information for the study of the gastrointestinal microbiome in bovines.

Comprehensive mouse microbiota genome catalog reveals major difference to its human counterpart.

Mouse is the most used model for studying the impact of microbiota on its host, but the repertoire of species from the mouse gut microbiome remains largely unknown. Accordingly, the similarity between human and mouse microbiomes at a low taxonomic level is not clear. We construct a comprehensive mouse microbiota genome (CMMG) catalog by assembling all currently available mouse gut metagenomes and combining them with published reference and metagenome-assembled genomes. The 41’798 genomes cluster into 1’573 species, of which 78.1% are uncultured, and we discovered 226 new genera, seven new families, and one new order. CMMG enables an unprecedented coverage of the mouse gut microbiome exceeding 86%, increases the mapping rate over four-fold, and allows functional microbiota analyses of human and mouse linking them to the driver species. Comparing CMMG to microbiota from the unified human gastrointestinal genomes shows an overlap of 62% at the genus but only 10% at the species level, demonstrating that human and mouse gut microbiota are largely distinct. CMMG contains the most comprehensive collection of consistently functionally annotated species of the mouse and human microbiome to date, setting the ground for analysis of new and reanalysis of existing datasets at an unprecedented depth.

Recovery of human gut microbiota genomes with third-generation sequencing

Human gut microbiota modulates normal physiological functions, such as maintenance of barrier homeostasis and modulation of metabolism, as well as various chronic diseases including type 2 diabetes and gastrointestinal cancer. Despite decades of research, the composition of the gut microbiota remains poorly understood. Here, we established an effective extraction method to obtain high quality gut microbiota genomes, and analyzed them with third-generation sequencing technology. We acquired a large quantity of data from each sample and assembled large numbers of reliable contigs. With this approach, we constructed tens of completed bacterial genomes in which there were several new bacteria species. We also identified a new conditional pathogen, Enterococcus tongjius, which is a member of Enterococci. This work provided a novel and reliable approach to recover gut microbiota genomes, facilitating the discovery of new bacteria species and furthering our understanding of the microbiome that underlies human health and diseases.

Identification of P-cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome

Identification of P-cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome

Metagenomic analysis of gut microbiota alteration in a mouse model exposed to mycotoxin deoxynivalenol

As one of the most prevalent contaminants in animal and human food, the deleterious effects of trichothecene mycotoxin deoxynivalenol (DON) warrant extensive investigation. Here, to assess the effects of DON exposure to the populations of gut microbiota, four-weeks-old mice were exposed to different doses (1.0 and 5.0 mg/kg) of DON every two days for 14 days. The contents of the cecum were then collected for DNA extraction and metagenomic shotgun sequencing, in order to detect alterations of the gut microbiota. We found that the average body weight and daily gain in the high dose DON treated group decreased. Metagenomic analysis demonstrated that the relative abundance of Firmicutes in the low and Bacteroidetes in the high dose groups increased compared to that in the untreated control group. Moreover, using gene calling and functional annotation, we found that large numbers of biosynthesis and degradation dependent populations were altered. As a result, metabolism pathways including sphingolipid, protein digestion/absorption, and lipoic acid pathways in the high dose DON exposed group dramatically fluctuated in comparison to the control and low dose groups. In addition, metagenomic binning identified ten microbiota genome drafts, with high levels of completeness, that further explain the DON-induced intestinal toxicity. Our findings suggested that DON exposure significantly impacted the microbiota community in the mouse, causing biosynthesis and degradation damage and metabolism pathway disorders.

The gut microbiome and heart failure.

The human gut is populated by a complex community of microbiota that coexists with the host to maintain homeostasis. Accumulating evidence shows that changes in the composition and diversity of gut microbiota, known as dysbiosis, is associated with cardiovascular diseases, such as atherosclerosis, hypertension, and heart failure. Although recent advances in biochemical and molecular analyses have contributed to the detection, identification, and characterization of a variety of gut microbiota genomes and their associated metabolites, the exact mechanisms of action remain unclear. As the prevalence of cardiovascular disease continues to rise, investigating the gut microbiome as a potential strategy for clinical intervention is highly warranted. In this review, we discuss correlations between the gut microbiome and heart failure, as well as the effects of altering the microbiome as a potential therapeutic target in cardiovascular diseases including heart failure.

The honey bee gut microbiota: strategies for study and characterization

Gut microbiota research is an emerging field that improves our understanding of the ecological and functional dynamics of gut environments. The honey bee gut microbiota is a highly rewarding community to study, as honey bees are critical pollinators of many crops for human consumption and produce valuable commodities such as honey and wax. Most significantly, unique characteristics of the Apis mellifera gut habitat make it a valuable model system. This review discusses methods and pipelines used in the study of the gut microbiota of Ap.mellifera and closely related species for four main purposes: identifying microbiota taxonomy, characterizing microbiota genomes (microbiome), characterizing microbiota-microbiota interactions and identifying functions of the microbial community in the gut. The purpose of this contribution is to increase understanding of honey bee gut microbiota, to facilitate bee microbiota and microbiome research in general and to aid design of future experiments in this growing field.

Possibility of treatment chronic adenoiditis and otitis media with effusion in children, into account the role of the microbiota of the mucous of the nasopharynx

In recent years, OME in childhood tends to increase. The low efficiency of the currently used traditional methods of conservative therapy and the high rate of relapse of the disease make it necessary to develop new methods of treatment. It is important that there is a connection of development of OME and hypertrophy of the lymphoid tissue of the nasopharynx, which in childhood is considered as a response to the respiratory antigenic virus-bacterial load. The spread of the inflammatory process to the auditory tube with persistence of pathogenic microorganisms in the structure of lymphoid tissue leads to the further development of otitis media effusion; but it is still debatable. All living microorganisms that inhabit a certain anatomical niche (viruses, bacteria, fungi, etc.) are called 'microbiota'. This term includes both commensals and pathogens. 'Microbiome' means the totality of all genes of all microorganisms that inhabit the study area. Thus, the microbiome can be called the collective microbiota genome. Microbiota disorder is a change in the quantitative and qualitative composition of microorganisms, called dysbiosis, and is important in the development of inflammatory pathology. Some drugs (including antibacterial ones) adversely affect indigenous bacteria. Indigenous microbiota develops in abundance in the observed biotope and forms resistance to excessive growth of pathogenic microorganisms. Only NGS sequencing allows to analyze entire mixed bacterial communities ('microbiomes'), which cannot be performed by other diagnostic methods. The use of the NGS sequencing method has proved the important role of microbiota in the development of chronic adenoiditis and OME in children. One of the promising remedies is the inclusion of lysozyme in the treatment regimen. Recent studies indicate the antibacterial and antiviral effects of lysozyme. The use of NGS sequencing made it possible to identify the relationship of the composition of microbiota with the course of chronic adenoiditis and otitis media effusion in children. Inclusion of lysozyme-containing drug Lizobact into therapy promotes colonization of the nasopharynx by indigenous microbiota, while the clinical picture improves.

The methicillin-resistant S. epidermidis strain RP62A genome mining for potential novel drug targets identification

In unique biofilm-forming methicillin-resistant (MRSE) strains of S. epidermidis have become a serious medical problem due to the emergence of antibiotic resistance strains. There is an essential need to develop novel drug targets to address the new intervention challenge for such multidrug-resistant bacteria. Here we utilized the available genomes and proteome datasets resources of MRSE S. epidermidis RP62A for comparative and subtractive genome analyses to identify novel drug targets for future drug discovery approaches. The comparative genome based molecular biology database resources scanning identified 255 proteins as essential human non-homologs targets for epidermidis RP62A that involve in essential metabolic pathways. Among these 12 targets were found to be involved in pathogen unique metabolic pathways. Druggability potential of each of these targets by Drug Bank database further identified 5 proteins as druggable essential proteins. As antimicrobial agents inflict beneficial gut microbiome and the antibiotics causes less agitation in gut flora are considered as best candidates. We pursued additional analysis and screen our lead targets proteins against metagenomes databases holding whole genome sequences of human gut microbiome. The negligible biological similarity with gut microbiota genomes datasets predicting the future implementation of our lead identified proteins as druggable targets for S. epidermidis RP62A that may not affect the essential humans gut microbiota. Based on these evidences, we are speculating that the putative druggable proteins addressed in this study are potent enough for their future evaluation as therapeutic targets to combat the S. epidermidis RP62A infections.

Microbiota: In Health and in Sickness, From Birth to Death.

Microorganisms colonize tissues and organs such as the skin and gastrointestinal, respiratory, and genitourinary systems. These microorganisms are generally called as "human microbiota". Human microbiota mostly consists of commensal microorganisms. The commensal microorganisms located on and in the human body are bacteria, fungi, viruses, archaea, and parasites. The microbiota genome is 100 times bigger in size than the human genome. Although the human genome is stationary, microbial genome has a compatible flexible variability during human life. As well as 2-year-old child and newborn, adult and adolescent, the elderly and pregnant woman have a different microbiota. Microbiota and the microbiota genome can be changed by personal and household diet, antibiotic use, mode of delivery, and hygiene within days or even hours, depending on such as these factors. The human immune system and microbiota grow up, develop, and mature as childhood friends by playing with each other from birth to death. Association between microbiota and human is not just related to childhood-it continues with health and disease, until death separates them. This review focused on the roles of microbiota in parasitology, autoimmune diseases, metabolic diseases, and cancer treatment in detail. In addition, inflammatory and immunoregulatory roles of microbiota on the intestinal immune system and how innate and adaptive immune systems regulate microbiota and its content were explained.

Constructing personalized longitudinal holo'omes of colon cancer-prone humans and their modeling in flies and mice.

Specific host genes and intestinal microbes, dysbiosis, aberrant immune responses and lifestyle may contribute to intestinal inflammation and cancer, but each of these parameters does not suffice to explain why sporadic colon cancer develops at an old age and only in some of the people with the same profile. To improve our understanding, longitudinal multi-omic and personalized studies will help to pinpoint combinations of host genetic, epigenetic, microbiota and lifestyle-shaped factors, such as blood factors and metabolites that change as we age. The intestinal holo’ome – defined as the combination of host and microbiota genomes, transcriptomes, proteomes, and metabolomes – may be imbalanced and shift to disease when the wrong host gene expression profile meets the wrong microbiota composition. These imbalances can be triggered by the dietary- or lifestyle-shaped intestinal environment. Accordingly, personalized human intestinal holo’omes will differ significantly among individuals and between two critical points in time: long before and upon the onset of disease. Detrimental combinations of factors could therefore be pinpointed computationally and validated using animal models, such as mice and flies. Finally, treatment strategies that break these harmful combinations could be tested in clinical trials. Herein we provide an overview of the literature and a roadmap to this end.

Does our gut microbiome predict cardiovascular risk? A review of the evidence from metabolomics.

Millions of microbes are found in the human gut, and are collectively referred as the gut microbiota. Recent studies have estimated that the microbiota genome contains 100-fold more genes than the host genome. These microbiota contribute to digestion by processing energy substrates unutilized by the host, with about half of the total genome of the gut microbiota being related to central carbon and amino acid metabolism as well as the biosynthesis of secondary metabolites. Therefore, the gut microbiome and its interaction with the host influences many aspects of health and disease, including the composition of biofluids such as urine and blood plasma. Metabolomics is uniquely suited to capture these functional host-microbe interactions. This review aims at providing an overview of recent metabolomics evidence of gut microbiota-host metabolic interactions with a specific focus on cardiovascular disease and related aspects of the metabolic syndrome. Furthermore, the emphasis is given on the complexities of translating these metabolite signatures as potential clinical biomarkers, as the composition and activity of gut microbiome change with many factors, particularly with diet, with special reference to trimethylamine-oxide.

Gut microbiota and metabolic diseases: myth or reality?

Microorganisms inhabiting human gastro-intestinal tract exceed the overall number of eukaryotic cells of about one order of magnitude [1–4]. Among the estimated 500–1,000 species [3], the majority has an unknown function, is neither beneficial nor harmful to host and represents the so-called ‘‘normal flora’’ or ‘‘microbiota’’ [5]. Noteworthy, the development of ‘‘next-generation’’ sequencing techniques, as part of the so-called ‘‘Omics’’, provided an holistic investigation allowing the study of the totality of gut microbiota, avoiding the need for lab-cultivation. These new molecular approaches opened the route toward a deeper investigation of the relationship between gut microbiota and host metabolism, focusing on multiple sides. Nowadays, Metagenomics [6, 7], Metatranscriptomics, Metabolomics [8] and Proteomics [9, 10] allow the study of gut microbiota genome, transcriptome and its impact on host metabolic profiles, respectively. In the last decade, an increasing attention has been paid on gut microbiota, given its involvement in functions other than digestion, as the etiology of inflammatory bowel diseases [11–13], autoimmunity [14–16], allergy [17] and even cancer [2]. However, the inner relationship between gut microbiota and host metabolism has been extensively investigated especially focusing on metabolic diseases [5, 18], even if the molecular actors underlying this inner link are yet to be fully understood. Gordon’s team performed pioneering studies using axenic (germfree) mice as a powerful model to study the impact of gut microbiota. Albeit these mice represent a non-physiologic model since the lack of gut microbiota impairs gut physiology [19], it has been shown that the establishment of a gut flora by colonization of axenic recipient mice with gut microbiota from donor mice is able to reverse this phenotype [20]. In addition, axenicity makes these mice resistant to dietinduced obesity, through a mechanism involving the enzyme lipoprotein lipase (LPL) and its inhibitor, the intestinal Fasting-induced adipocyte factor (Fiaf), which is over-activated in germfree conditions. This results in a diminished capacity to harvest energy from nutrients [21]. Gut microbiota ecology has been shown as deeply unbalanced in relation to metabolic diseases and on the top of it, obesity. The division of Firmicutes, a major phylum of gut microbiota in adulthood [22], has been positively correlated to body weight gain and obesity [23, 24]. Conversely, the division of Bacteroidetes, the second most represented phylum of gut bacterial ecology, characterizes a lean phenotype, both in humans and mice [23, 24]. Gordon’s team was even the first to show the transmissibility of obesity by transferring its microbial component (gut microbiota issued from obese mice) into axenic recipient and showing an increased adipose tissue development when compared to recipient mice colonized with gut microbiota issued from lean mice [25]. However, metabolic diseases are always associated with a low-grade chronic inflammation in metabolically active tissues [26, 27]. Therefore, in the quest of a missing link between gut microbiota and inflammation, Burcelin’s team was the first to link inflammation to intestinal microbiota and metabolic diseases by showing that an increase in lipopolysaccharides (LPS) plasma levels (referred to as ‘‘metabolic endotoxemia’’) was the initiator of metabolic M. Serino (&) R. Burcelin Institut National de la Sante et de la Recherche Medicale (INSERM), U858, Toulouse, France e-mail: matteo.serino@inserm.fr

The evolution of animals and plants via symbiosis with microorganisms

Animals and plants evolved from prokaryotes and have remained in close association with them. We suggest that early eukaryotic cells, formed by the fusion of two or more prokaryotes, already contained prokaryotic genetic information for aggregation and the formation of multicellular structures. The hologenome theory of evolution posits that a unit of selection in evolution is the holobiont (host plus symbionts). The hologenome is defined as the genetic information of the host and its microbiota, which function in consortium. Genetic variation of the holobiont, the raw material for evolution, can arise from changes in either the host or the symbiotic microbiota genomes. Changes in the hologenome can occur by two processes that are specific to holobionts: microbial amplification and acquisition of novel strains from the environment. Recent data from culture-independent studies provides considerable support of the hologenome theory: (i) all animals and plants contain abundant and diverse microbiota, (ii) the symbiotic microbiota affects the fitness of their host and (iii) symbiotic microorganisms are transmitted from parent to offspring. Consideration of the dynamic aspects of symbioses of hosts with their diverse microbiota leads to the conclusion that holobionts can evolve not only via Darwinian but also by adaptive Lamarckian principles.