Gut Microbiota in Obesity and Undernutrition de Clercq, Nicolien C; Groen, Albert K; Romijn, Johannes A ...
Advances in nutrition (Bethesda, Md.),
11/2016, Volume:
7, Issue:
6
Journal Article
Peer reviewed
Open access
Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the ...onset and preservation of malnutrition. One of these factors is the gut microbiota, which has been recognized as an important pathophysiologic factor in the development and sustainment of malnutrition. However, to our knowledge, the extent to which the microbiota influences malnutrition has yet to be elucidated. In this review, we summarize the mechanisms via which the gut microbiota may influence energy homeostasis in relation to malnutrition. In addition, we discuss potential therapeutic modalities to ameliorate obesity or undernutrition.
Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host ...metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome.
A selective literature review was conducted to evaluate GI and brain interactions.
Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear.
One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.
Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies ...in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders.
Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential ...microbial-metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn.
Introduction: Malnutrition refers to both over- and undernutrition and results from a disruption in energy balance. It affects one in three people worldwide and is associated with increased morbidity ...and mortality. The intestinal microbiota represents a newly identified factor that might contribute to the development of malnutrition, as it harbors traits that complement the human metabolic and endocrine capabilities, thereby influencing energy balance.
Areas covered: In the current review, we aim to give a comprehensive overview on the microbiota, its development and its possible influence on energy balance, with emphasis the role of short-chain fatty acids. We also consider microbial characteristics associated with obesity and undernutrition and evaluate microbial manipulating strategies. The PubMed database was searched using the terms: 'gastrointestinal microbiota', 'volatile fatty acids', 'malnutrition', 'undernutrition', 'obesity', 'insulin resistance', 'prebiotics', 'probiotics', 'antibiotics' and 'fecal microbiota transplantation'.
Expert commentary: Microbiota make important contributions to the regulation of energy balance, whereas microbial disturbances might predispose to malnutrition. If we manage to manipulate the microbiota to our benefit, it could lead to preventive or therapeutic strategies targeting malnutrition.
Context/Objective: In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic–euglycemic (HE) clamps in ...individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers. Design/Methods: In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd). Machine learning models and conventional statistics were used to identify biomarkers of insulin resistance. Findings were replicated in a cohort with n = 282 obese men and women with (n = 156) and without (n = 126) MetSyn. In addition to this, the relation between biomarkers and adipose tissue was assessed by nuclear magnetic resonance imaging. Results: Peripheral insulin resistance is marked by changes in proteins related to inflammatory processes such as IL-1 and TNF-receptor and superfamily members. These proteins can distinguish between insulin-resistant and insulin-sensitive individuals (AUC = 0.72 ± 0.10) with MetSyn. These proteins were also associated with IFG, liver fat (rho 0.36, p = 1.79 × 10−9) and visceral adipose tissue (rho = 0.35, p = 6.80 × 10−9). Interestingly, these proteins had the strongest association in the MetSyn subgroup compared to individuals without MetSyn. Conclusions: MetSyn associated with insulin resistance is characterized by protein changes related to body fat content, insulin signaling and pro-inflammatory processes. These findings provide novel targets for intervention studies and should be the focus of future in vitro and in vivo studies.
The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in ...the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome.
With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects.
This study was performed to evaluate the long-term impact of maxillomandibular advancement (MMA) surgery on the apnoea–hypopnoea index (AHI) and quality of life (QoL) in patients with obstructive ...sleep apnoea syndrome (OSAS). The medical files of 12 OSAS patients who underwent MMA by one surgeon between 1995 and 1999 were reviewed retrospectively. Patients received a clinical assessment, polysomnography, and QoL questionnaires as part of routine care preoperatively (n=12), within 2 years postoperative (n=12), and again in 2016 (n=9). A successful surgical outcome was defined as an AHI decrease of >50% with <20 events/h. Of the 66.7% (8/12) of patients who were initially cured, 66.7% (4/6) remained stable at a median follow-up of 19 years. Only the two patients with the highest AHI showed abnormal Epworth Sleepiness Scale scores. After convalescence, most patients reported stable symptomatic improvement. Aesthetic changes were found acceptable and all but one patient stated that they would undergo the surgery again. It is concluded that MMA is a safe and effective procedure. Ageing and weight gain might counterbalance the positive effects of surgery in the long term. It is therefore suggested that re-evaluation every 5 years should be scheduled, since a spontaneous AHI increase over time does not seem to be reflected by symptomatic changes.
The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of ...nCRT combined with programmed-death ligand-1 (PD-L1) inhibition for rEAC.
Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1,200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score-matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies.
We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (
= 4), patient choice (
= 2), and death (
= 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNγ signature was higher in responders compared with nonresponders (
= 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs.
Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.
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