Fecal Metaproteomics Reveals Reduced Gut Inflammation and Changed Microbial Metabolism Following Lifestyle-Induced Weight Loss

Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of metabolic syndrome. To investigate if lifestyle-induced weight loss (WL) may modulate the gut microbiome composition and its interaction with the host on a functional level, we analyzed the fecal metaproteome of 33 individuals with metabolic syndrome in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort. The 6-month WL intervention resulted in reduced BMI (−13.7%), improved insulin sensitivity (HOMA-IR, −46.1%), and reduced levels of circulating hsCRP (−39.9%), indicating metabolic syndrome reversal. The metaprotein spectra revealed a decrease of human proteins associated with gut inflammation. Taxonomic analysis revealed only minor changes in the bacterial composition with an increase of the families Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae and Verrucomicrobiaceae. Yet we detected an increased abundance of microbial metaprotein spectra that suggest an enhanced hydrolysis of complex carbohydrates. Hence, lifestyle-induced WL was associated with reduced gut inflammation and functional changes of human and microbial enzymes for carbohydrate hydrolysis while the taxonomic composition of the gut microbiome remained almost stable. The metaproteomics workflow has proven to be a suitable method for monitoring inflammatory changes in the fecal metaproteome.

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Abstract P033: Relationship Between Adiponectin Level and Metabolic Syndrome after Weight Loss in Patients with Abdominal Obesity

Circulation ◽

10.1161/circ.127.suppl_12.ap033 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Aelita Berezina ◽

Olga Belyaeva ◽

Olga Berkovich ◽

Elena Baranova ◽

Tatyina Karonova

Keyword(s):

Metabolic Syndrome ◽

Weight Loss ◽

Abdominal Obesity ◽

Metabolic Disorders ◽

Intervention Program ◽

Adiponectin Level ◽

The Metabolic Syndrome ◽

Outpatient Intervention ◽

Before And After ◽

The Relationship

Objective: to investigate the relationship between adiponectin level and metabolic syndrome (MS) after weight loss in patients with abdominal obesity (AO). Method: A 3-year randomized lifestyle intervention trial performed in 153 patients with AO, age 43,2±0,8 yrs, BMI 32,1±1,9 kg/m 2 . 74 patients keep hypocaloric diet (gr.1), 79 patients keep diet and performed aerobic exercise (gr.2). Adiponectin concentration, body mass (BM), waist circumference (WC), body fat (BF), BMI, the levels of BP, glucose, insulin, HOMA-IR, TC, HDL-C, LDL-C, TG, CRP were measured before and after a 3-years outpatient intervention program. Results. 100% patients with AO had some metabolic disorders and 38% had MS before the treatment. The adiponectin levels and others parameters didn’t differ between the groups before intervention (p>0,05). In 3 years 53 (71,6%) and 58 (73,4%) patients from 1 and 2 groups reduced weight. The rate of improving BM, BMI, BF, WC, HDL-C, TG and insulin was grater in patients gr.2 (p<0,05). The favorable dynamics of MS (MS didn’t appeared at the end of study or didn’t registered in patients who had it before) didn’t differ between the groups 1 and 2 (81,1% and 91,4%, p>0,05). The increasing of adiponectin level occurred more often in patients gr.2, than gr.1 (93,1% and 58,5%, p=0,001, respectively). Adiponectin level increased only in patients gr.2 (18,0±1,1mcg/ml and 23,8±1,3 mcg/ml, p= [[Unable to Display Character: р]]=0,0001), didn’t changed in gr.1 (p>0,05). It was established that in patients with combination of weight loss and increasing of adiponectin level favorable dynamics of MS occurred more often than in patients who lost weight without increasing of adiponectin level (91,7% and 69,2%, p=0,0001). In patients with favorable dynamics of MS increasing of adiponectin level had met more often, than in patients with unfavorable dynamics of MS (MS continued or appeared) (88,6% and 11,4%, p=0,0001). Increasing of adiponectin level associated with positive dynamics of the MS - OR=9,1 (4,0-20,6). Conclusion. Combination of weight loss and increasing of adiponectin level associated with favorable dynamics of the metabolic syndrome.

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Posttraumatic Stress Disorder and the Gut Microbiome

The Oxford Handbook of the Microbiome-Gut-Brain Axis ◽

10.1093/oxfordhb/9780190931544.013.10 ◽

2020 ◽

Author(s):

Kelsey M. Loupy ◽

Christopher A. Lowry

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Gut Microbiome ◽

Stress Disorder ◽

Individual Variability ◽

Low Grade ◽

Related Disorder ◽

Microbiome Composition ◽

Glucocorticoid Signaling ◽

System Functioning

Posttraumatic stress disorder (PTSD) is a trauma- and stressor-related disorder that is often associated with the dysregulation of multiple physiological systems, including autonomic nervous system functioning, glucocorticoid signaling, and chronic low-grade inflammation. Recent evidence suggests that persons with a diagnosis of PTSD also exhibit alterations in the composition of gut microbiomes compared to people who are trauma-exposed but do not develop PTSD. The bidirectional communication between the gut microbiome, the gut, and the brain, deemed the microbiome-gut-brain (MGB) axis, is composed of neural, neuroendocrine, and immune processes that both impact and respond to the structure of the gut microbiome. This chapter aims to outline (1) the ways in which trauma and stressor exposure may impact the gut microbiome; (2) the ways in which gut microbiome composition may influence brain function, including anxiety, and fear responses; and (3) how the bidirectional MGB axis, through interactions with several physiological circuits, may determine individual variability in resilience versus vulnerability to development of PTSD after trauma exposure.

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Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

10.7287/peerj.preprints.1754v1 ◽

2016 ◽

Author(s):

Melissa N. Conley ◽

Carmen P. Wong ◽

Kyle M. Duyck ◽

Norman Hord ◽

Emily Ho ◽

...

Keyword(s):

Immune System ◽

Murine Model ◽

Gut Microbiome ◽

Inflammatory Marker ◽

Low Grade ◽

Host Immune System ◽

Cancer Type ◽

Microbiome Composition ◽

Aged Mice ◽

Age Related

Introduction Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as “inflammaging”. While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of the study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age, and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 also stratify individuals by age. Discussion Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age, relative abundance of specific taxa in the gut microbiome, and serum MCP-1 status in mice indicates that the gut microbiome may play a modulating role in age-related inflammatory processes. These findings warrant further investigation of taxa associated with the inflammaging phenotype and the role of gut microbiome in the health status and immune function of aged individuals.

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Interplay between the human gut microbiome and host metabolism

10.1101/561787 ◽

2019 ◽

Cited By ~ 1

Author(s):

Alessia Visconti ◽

Caroline I. Le Roy ◽

Fabio Rosa ◽

Niccolo Rossi ◽

Tiphaine C. Martin ◽

...

Keyword(s):

Gut Microbiome ◽

Metabolic Pathways ◽

Taxonomic Composition ◽

Metagenomic Sequencing ◽

Human Gut ◽

Metabolic Potential ◽

Microbial Ecosystem ◽

Microbiome Composition ◽

Shotgun Metagenomic Sequencing ◽

Key Species

AbstractThe human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

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Markers of inflammation and insulin resistance in dogs before and after weight loss versus lean healthy dogs

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-6245 ◽

2020 ◽

Vol 40 (4) ◽

pp. 300-305

Author(s):

Juliana T. Jeremias ◽

Thiago H.A. Vendramini ◽

Roberta B.A. Rodrigues ◽

Mariana P. Perini ◽

Vivian Pedrinelli ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Body Fat ◽

Peptide Yy ◽

Body Condition Score ◽

Weight Loss Program ◽

Control Group ◽

Low Grade ◽

Markers Of Inflammation ◽

Before And After

ABSTRACT: Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory cytokines that contribute to insulin resistance. For this study body composition, markers of inflammation and of insulin resistance in dogs before and after weight loss were compared to those of lean dogs. Eleven client-owned obese adult dogs underwent a weight loss program with commercial dry food for weight loss and reached an ideal body condition score (BCS) six months after the beginning of the weight loss program. A Control Group of nine dogs with ideal BCS were selected for the comparison. Shapiro-Wilk test was used to test for normality, Mann Whitney were used for non-normally distributes data, and Student t-test was used for normally distributed parameters. In the Obese Group body fat decreased from 41.6% (30.7-58.6) to 29.1% (18.6-46.3) (P<0.01) and dogs maintained lean body mass throughout the weight loss program (P>0.05). Obese dogs presented higher concentration of fructosamine, triglycerides, insulin, IGF-1 and leptin than the Control Group before weight reduction (P<0.05). Serum concentrations of triglycerides, IL-2, IL-6, TNF-α, insulin, leptin and IGF-1 decreased after weight loss (P<0.01), and these concentrations were similar to the Control Group (P>0.05), except for leptin (P<0.001). No alteration on peptide YY was found. Leptin (r=0.60, P=0.01), fructosamine (r=0.44, P=0.02) and triglycerides (r=0.40, P=0.04) concentrations correlated with the reduction of body fat. Weight loss reduced the concentrations of inflammatory and insulin resistance markers and most parameters became similar to dogs that have always been lean, reinforcing the importance of weight loss in small animal practice.

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Metformin Strongly Affects Gut Microbiome Composition in High-Fat Diet-Induced Type 2 Diabetes Mouse Model of Both Sexes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.626359 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laila Silamiķele ◽

Ivars Silamiķelis ◽

Monta Ustinova ◽

Zane Kalniņa ◽

Ilze Elbere ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiome ◽

High Fat Diet ◽

Abundant Species ◽

Metformin Treatment ◽

High Fat ◽

Microbiome Composition ◽

Before And After ◽

Diabetes Mouse

Effects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mouse models, depending on sex and metabolic status in well controlled experimental setting. Our study aimed to examine metformin-induced alterations in gut microbiome diversity, composition, and functional implications of high-fat diet-induced type 2 diabetes mouse model, using, for the first time in mice study, the shotgun metagenomic sequencing that allows estimation of microorganisms at species level. We also employed a randomized block, factorial study design, and including 24 experimental units allocated to 8 treatment groups to systematically evaluate the effect of sex and metabolic status on metformin interaction with microbiome. We used DNA obtained from fecal samples representing gut microbiome before and after ten weeks-long metformin treatment. We identified 100 metformin-related differentially abundant species in high-fat diet-fed mice before and after the treatment, with most of the species relative abundances increased. In contrast, no significant changes were observed in control diet-fed mice. Functional analysis targeted to carbohydrate, lipid, and amino acid metabolism pathways revealed 14 significantly altered hierarchies. We also observed sex-specific differences in response to metformin treatment. Males experienced more pronounced changes in metabolic markers, while in females the extent of changes in gut microbiome representatives was more marked, indicated by 53 differentially abundant species with more remarkable Log fold changes compared to the combined-sex analysis. The same pattern manifested regarding the functional analysis, where we discovered 5 significantly affected hierarchies in female groups but not in males. Our results suggest that both sexes of animals should be included in future studies focusing on metformin effects on the gut microbiome.

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Appetite Control Might not Be Improved after Weight Loss in Adolescents with Obesity, Despite Non-Persistent Metabolic Syndrome

Nutrients ◽

10.3390/nu12123885 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3885

Author(s):

Valérie Julian ◽

Laurie Isacco ◽

Marwa Khammassi ◽

Alicia Fillon ◽

Maud Miguet ◽

...

Keyword(s):

Metabolic Syndrome ◽

Weight Loss ◽

Body Composition ◽

Energy Intake ◽

Weight Loss Intervention ◽

Appetite Control ◽

Post Intervention ◽

The Metabolic Syndrome ◽

Daily Energy ◽

Before And After

The aim of this study was to evaluate the effect of a multidisciplinary weight loss intervention on energy intake and appetite sensations in adolescents with obesity, depending on the initial diagnosis or persistence of the metabolic syndrome. Ninety-two adolescents with obesity (12–15 years) followed a 16-week multidisciplinary weight loss intervention. Anthropometric and body composition characteristics, metabolic profile, ad libitum daily energy intake, and appetite sensations were assessed before and after the intervention. The presence of metabolic syndrome (MS) was determined at baseline (MS vs. non-MS) and after the program (persistent vs. non-persistent). While the intervention was effective in inducing weight loss (body weight T0: 87.1 ± 14.9 vs. T1: 81.2 ± 13.0 kg; p < 0.001) and body composition improvements in both adolescents with and without MS, energy intake (p = 0.07), hunger (p = 0.008), and prospective food consumption (p = 0.03) increased, while fullness decreased (p = 0.04) in both groups. Energy intake and appetite were not improved in non-persistent MS after the program and remained significantly higher among non-persistent adolescents compared with initially non-MS adolescents. To conclude, appetite control seems impaired in obese adolescents, irrespective of being affected by MS or not, whereas the treatment of MS in this population might fail to effectively preclude the adolescents from potential post-intervention compensatory food intake and subsequent weight regain.

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