Understanding immune-microbiota interactions in the intestine.

Published on Jan 1, 2020in Immunology5.016
· DOI :10.1111/IMM.13150
Philip P. Ahern20
Estimated H-index: 20
(Cleveland Clinic Lerner Research Institute),
Kevin J. Maloy45
Estimated H-index: 45
(Glas.: University of Glasgow)
The past two decades have seen an explosion in research that aims to understand how the dynamic interplay with the gut microbiota impacts host health and disease, establishing a role for the gut microbiota in a plethora of pathologies. Understanding how health‐promoting microbiota are established and how beneficial host–microbiota interactions are maintained is of immense biomedical importance. Despite the enormous progress that has been made, our knowledge of the specific microbiota members that mediate these effects and the mechanisms underlying these interactions is rudimentary. The dearth of information regarding the nature of advantageous host–microbiota interactions, and the factors that cause these relationships to go awry, has hampered our ability to realize the therapeutic potential of the microbiota. Here we discuss key issues that limit current knowledge and describe a path forwards to improving our understanding of the contributions of the microbiota to host health.
📖 Papers frequently viewed together
30 Citations
49 Citations
27 Citations
#1Ziad Al Nabhani (French Institute of Health and Medical Research)H-Index: 9
#2Sophie Dulauroy (French Institute of Health and Medical Research)H-Index: 9
Last. Gérard Eberl (French Institute of Health and Medical Research)H-Index: 71
view all 10 authors...
Summary Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response—a “weani...
110 CitationsSource
#1Tzu-Yu Shao (Cincinnati Children's Hospital Medical Center)H-Index: 4
#2W.X. Gladys Ang (Cincinnati Children's Hospital Medical Center)H-Index: 2
Last. Sing Sing Way (Cincinnati Children's Hospital Medical Center)H-Index: 37
view all 13 authors...
Summary Mucosal barriers are densely colonized by pathobiont microbes such as Candida albicans, capable of invasive disseminated infection. However, systemic infections occur infrequently in healthy individuals, suggesting that pathobiont commensalism may elicit host benefits. We show that intestinal colonization with C. albicans drives systemic expansion of fungal-specific Th17 CD4+ T cells and IL-17 responsiveness by circulating neutrophils, which synergistically protect against C. albicans in...
60 CitationsSource
#1Mark S. Ladinsky (California Institute of Technology)H-Index: 26
#2Leandro Pires Araujo (Columbia University)H-Index: 2
Last. Ivaylo I. Ivanov (Columbia University)H-Index: 34
view all 20 authors...
INTRODUCTION Although commensal microbes populate our barrier surfaces without causing obvious disease, they nonetheless modulate host physiology and immunity. Commensal bacteria can regulate host T cell differentiation and function, and a large fraction of mucosal tissue-resident T cells are thought to recognize commensal antigens, which triggers the T cells’ participation in the maintenance of mucosal homeostasis. Therefore, the mechanisms by which commensal antigens or other microbiota-derive...
51 CitationsSource
#1Julie Schulthess (University of Oxford)H-Index: 3
#2Sumeet Pandey (John Radcliffe Hospital)H-Index: 10
Last. Fiona Powrie (University of Oxford)H-Index: 97
view all 15 authors...
Summary Host microbial cross-talk is essential to maintain intestinal homeostasis. However, maladaptation of this response through microbial dysbiosis or defective host defense toward invasive intestinal bacteria can result in chronic inflammation. We have shown that macrophages differentiated in the presence of the bacterial metabolite butyrate display enhanced antimicrobial activity. Butyrate-induced antimicrobial activity was associated with a shift in macrophage metabolism, a reduction in mT...
173 CitationsSource
#1Marta Wegorzewska (WashU: Washington University in St. Louis)H-Index: 2
#2Robert W. P. Glowacki (UM: University of Michigan)H-Index: 7
Last. Paul M. Allen (WashU: Washington University in St. Louis)H-Index: 11
view all 9 authors...
T cell responses to symbionts in the intestine drive tolerance or inflammation depending on the genetic background of the host. These symbionts in the gut sense the available nutrients and adapt their metabolic programs to use these nutrients efficiently. Here, we ask whether diet can alter the expression of a bacterial antigen to modulate adaptive immune responses. We generated a CD4 + T cell hybridoma, BθOM, specific for Bacteroides thetaiotaomicron ( B. theta ). Adoptively transferred transge...
22 CitationsSource
#1Masayuki Fujii (Keio: Keio University)H-Index: 12
#2Hans Clevers (UU: Utrecht University)H-Index: 205
Last. Toshiro Sato (Keio: Keio University)H-Index: 57
view all 3 authors...
Insights into the stem cell niche have allowed researchers to cultivate adult tissue stem cells as organoids that display structural and phenotypic features of healthy and diseased epithelial tissues. Organoids derived from patients' tissues are used as models of disease and to test drugs. CRISPR-Cas9 technology can be used to genetically engineer organoids for studies of monogenic diseases and cancer. We review the derivation of organoids from human gastrointestinal tissues and how CRISPR-Cas9 ...
40 CitationsSource
#1Samuel C. Forster (Monash University, Clayton campus)H-Index: 23
#2Nitin KumarH-Index: 18
Last. Trevor D. LawleyH-Index: 55
view all 17 authors...
Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial geno...
168 CitationsSource
#1Takeshi Tanoue (Keio: Keio University)H-Index: 9
#2Satoru Morita (Keio: Keio University)H-Index: 2
Last. Kenya Honda (Keio: Keio University)H-Index: 74
view all 28 authors...
There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing in...
280 CitationsSource
#1Edoardo Pasolli (University of Trento)H-Index: 29
#2Francesco Asnicar (University of Trento)H-Index: 21
Last. Nicola Segata (University of Trento)H-Index: 61
view all 18 authors...
Summary The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled sampl...
396 CitationsSource
#1Graham J. Britton (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 13
#2Eduardo J. Contijoch (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 7
Last. Jeremiah J. Faith (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 35
view all 21 authors...
Summary Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers ...
118 CitationsSource
Cited By27
#1He Zhang (Harbin Veterinary Research Institute)H-Index: 1
#2Ma Wenjie (Harbin Veterinary Research Institute)
Last. Yue Wang (Harbin Veterinary Research Institute)H-Index: 19
view all 11 authors...
Increasing evidence shows that gut microbiota plays a critical role in host immune system development and immune regulation, thus the composition of gut microbiota may affect how individuals respond to immunizations. Currently, little evidence is available on the correlation between porcine gut microbiota and vaccine immune response. Here, we investigated the influence of gut microbiota on immune response in pigs to porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Based on th...
#1Elena Gonçalves (University of Paris)H-Index: 3
#2Yolanda GuillénH-Index: 8
Last. Béhazine Combadière (University of Paris)H-Index: 32
view all 7 authors...
The identification of new biomarkers is essential to predict responsiveness to vaccines. We investigated the whole-blood transcriptome and microbiome prior to immunization, in order to assess their involvement in induction of humoral responses two months later. We based our analyses on stool and skin microbiota, and blood transcriptome prior to immunization, in a randomized clinical study in which participants were vaccinated with the MVA-HIV clade B vaccine (MVA-B). We found that the levels of ...
#1Xiaolin LiuH-Index: 1
#2Min Dai (Nanjing Medical University)H-Index: 4
Last. Jun WangH-Index: 210
view all 13 authors...
Abstract The human gut microbiome has primarily been studied through the use of fecal samples, a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities. However, this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract (in situ), and the infrequent availability of fecal samples prevents analysis at finer temporal scales (e.g., hours). In our study...
#1Noëmie Daniel (University of Paris)
#2Emelyne Lécuyer (Pasteur Institute)H-Index: 6
Last. Benoit Chassaing (University of Paris)H-Index: 2
view all 3 authors...
During the last 20 years, a new field of research delineating the importance of the microbiota in health and diseases has emerged. Inappropriate host-microbiota interactions have been shown to trigger a wide range of chronic inflammatory diseases, and defining the exact mechanisms behind perturbations of such relationship, as well as ways by which these disturbances can lead to disease states, both remain to be fully elucidated. The mucosa-associated microbiota constitutes a recently studied mic...
#1Panayiotis Louca ('KCL': King's College London)H-Index: 3
#2Benjamin J. Murray ('KCL': King's College London)H-Index: 47
Last. Cristina Menni ('KCL': King's College London)H-Index: 54
view all 26 authors...
Objectives Dietary supplements may ameliorate SARS-CoV-2 infection, although scientific evidence to support such a role is lacking. We investigated whether users of the COVID-19 Symptom Study app who regularly took dietary supplements were less likely to test positive for SARS-CoV-2 infection. Design App-based community survey. Setting 445 850 subscribers of an app that was launched to enable self-reported information related to SARS-CoV-2 infection for use in the general population in the UK (n...
#1Selma P. Wiertsema (UU: Utrecht University)H-Index: 17
#1Selma P. WiertsemaH-Index: 1
Last. Léon M.J. KnippelsH-Index: 35
view all 4 authors...
Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal imm...
#1Allan McI. Mowat (Glas.: University of Glasgow)H-Index: 59
Metchnikoff's essay, Intestinal Bacteriotherapy, was written when the study of microbiology was still in its infancy and few intestinal diseases had been ascribed to a specific bacterial infection. Metchnikoff offered perceptive ideas that have become standard in today's science. This Historical Perspectives commentary examines how Metchnikoff's article influenced our field. An accompanying editorial by Siamon Gordon explores this topic further and describes the relevance of Metchnikoff's work t...
#1Kathy D. McCoy (U of C: University of Calgary)H-Index: 58
#2Christina L. Ohland (U of C: University of Calgary)H-Index: 3
The intestinal microbiota is comprises a diverse community of micro-organisms that interact with many host processes. Innate immune responses to the gut microbiota are of particular importance as they influence many other downstream responses. This fascinating host–microbe crosstalk is a rapidly expanding field of study; thus, it is critical to ensure reproducibility between studies and applicability to human clinical trials through standardization of experiments. We discuss here recent advances...
#1Jing Tang (ZJU: Zhejiang University)H-Index: 12
#2Xianglu Wu (CQMU: Chongqing Medical University)H-Index: 1
Last. Feng Zhu (ZJU: Zhejiang University)H-Index: 68
view all 14 authors...
Besides the environmental factors having tremendous impacts on the composition of microbial community, the host factors have recently gained extensive attentions on their roles in shaping human microbiota. There are two major types of host factors: host genetic factors (HGFs) and host immune factors (HIFs). These factors of each type are essential for defining the chemical and physical landscapes inhabited by microbiota, and the collective consideration of both types have great implication to se...
5 CitationsSource