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Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease pp 291–317Cite as

Microbiota, Inflammation and Obesity

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Part of the book series: Advances in Experimental Medicine and Biology ((MICENDO,volume 817))

Abstract

Interactions between metabolism and immunity play a pivotal role in the development of obesity-associated chronic co-morbidities. Obesity involves impairment of immune function affecting both the innate and adaptive immune system. This leads to increased risk of infections as well as chronic low-grade inflammation, which in turn causes metabolic dysfunction (e.g. insulin resistance) and chronic disease (e.g. type-2 diabetes). Gut microbiota has emerged as one of the key factors regulating early events triggering inflammation associated with obesity and metabolic dysfunction. This effect seems to be related to diet- and obesity-associated changes in gut microbiota composition and to increased translocation of immunogenic bacterial products, which activate innate and adaptive immunity in the gut and beyond, contributing to an increase in inflammatory tone. Innate immune receptors, like Toll-like receptors (TLRs), are known to be up-regulated in the tissue affected by most inflammatory disorders and activated by both specific microbial components and dietary lipids. This triggers several signaling transduction pathways (e.g. JNK and IKKβ/NF-κB), leading to inflammatory cytokine and chemokine (TNF-α, IL-1, MCP1) production and to inflammatory cell recruitment, causing insulin resistance. T-cell differentiation into effector inflammatory or regulatory T cells also depends on the type of TLR activated and on cytokine production, which in turn depends upon gut microbiota-diet interactions. Here, we update and discuss our current understanding of how gut microbiota could contribute to defining whole-body metabolism by influencing diverse components of the innate and adaptive immune system, both locally and systemically.

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Abbreviations

BMI:

Body mass index

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

ERS:

Endoplasmic reticulum stress

FetA:

Fetuin-A

HFD:

High-fat diet

IKK:

Inhibitory κB kinase

IL:

Interleukin

IL-1Ra:

IL-1 receptor antagonist

iNOS:

Inducible nitric oxide synthase

IR:

Insulin receptor

IRF:

Interferon regulatory transcription factor

IRS:

Insulin receptor substrate

IRS-1:

Insulin receptor substrate 1

LPS:

Lipopolysaccharide

LTA:

Lipoteichoic acids

M1:

“Classically activated” macrophages

M2:

“Alternative activated” macrophages

MAPKs:

Mitogen-activated protein kinases

M-cells:

Microfold cells

MCP:

Monocyte chemotactic protein

MDP:

Muramyl dipeptide

Meso-DAP:

d-Glutamyl-meso-diaminopimelic acid

MHC:

Major histocompatibility complex

NF- κB:

Nuclear factor-κB

NKT:

Natural killer T

NLRs:

Nod-like receptor family

NOD:

Nucleotide oligomerization domain

NOS2:

Nitric-oxide synthase 2

PGN:

Peptidoglycan

PI3K:

Phosphatidylinositol 3-kinase

PI3-K:

Phosphatidylinositol 3-kinase

RHM:

Recruited hepatic macrophage

ROS:

Reactive oxygen species

SAA3:

Serum amyloid A3 protein

SFA:

Saturated fatty acid

SOC:

Suppressor of cytokine signaling

STAT3:

Signal transducer and activator of transcription 3

TH1:

T helper 1

TLRs:

Toll-like receptor family

TNF:

Tumor necrosis factor

Tregs:

Regulatory T

ZO:

Zonula occludens

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Acknowledgements

This work was supported by grants AGL2011-25169 and Consolider Fun-C-Food CSD2007-00063 from the Spanish Ministry of Economy and Competitiveness (MINECO, Spain). The scholarship of A Moya from MINECO is fully acknowledged.

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Authors and Affiliations

  1. Microbial Ecology, Nutrition & Health, National Research Council (IATA-CSIC), Av. Agustín Escardino 7, 46980, Paterna, Valencia, Spain

    Yolanda Sanz & Angela Moya-Pérez

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  1. Yolanda Sanz
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  2. Angela Moya-Pérez
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Correspondence to Yolanda Sanz .

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Editors and Affiliations

  1. Immunotherapeutics and Biotechnology, Texas Tech University Health Sciences Center, Abilene, Texas, USA

    Mark Lyte

  2. Department of Anatomy and Neuroscience, University College, Cork, Cork, Ireland

    John F. Cryan

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Sanz, Y., Moya-Pérez, A. (2014). Microbiota, Inflammation and Obesity. In: Lyte, M., Cryan, J. (eds) Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. Advances in Experimental Medicine and Biology(), vol 817. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0897-4_14

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