Exercise Training Reverses Gut Dysbiosis in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis: A Proof of Concept Study

Hughes, Alexa J; Dahmus, Jessica; Rivas, Gloriany; Hummer, Breianna; See, Jeremy R. Chen; Wright, Justin; Lamendella, Regina; Schmitz, Kathryn H.; Sciamanna, Christopher N.; Patterson, Andrew D.; Loomba, Rohit; Stine, Jonathan G.

doi:10.1016/j.cgh.2020.08.063

Cited by 14 publications

(17 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PAI-1 is also produced in gut epithelial and subepithelial cells, increasing the possibility Open access of unique roles in gastrointestinal function and energy balance. 29 And while we did not specifically measure PAI-1 in our proof of concept study, this is an intriguing line of study as to our knowledge, whether lifestyle alterations focusing on dietary regimens, physical activity and weight loss can lead to a reduction in PAI-1 through loss of adipocytes remains unknown in patients with NASH.…”

Section: Discussionmentioning

confidence: 93%

Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis

Rivas

Hummer-Bair

Bezinover

et al. 2021

BMJ Open Gastroenterol

Self Cite

View full text Add to dashboard Cite

BackgroundNon-alcoholic fatty liver disease is a prohaemostatic state with abnormal primary, secondary and tertiary haemostasis. Plasminogen activator inhibitor (PAI)-1 is the best-established marker for prohaemostasis in non-alcoholic fatty liver disease. While epidemiological studies demonstrate decompensated non-alcoholic steatohepatitis (NASH) cirrhosis patients have increased rates of venous thromboembolism, including portal vein thrombosis, mechanistic studies have focused exclusively on patients without or with compensated cirrhosis. We aimed to characterizecharacterise PAI-1 levels in decompensated NASH cirrhosis.MethodsPAI-1 level was measured in consecutive adult liver transplant recipients immediately prior to liver transplantation. Multivariable models were constructed using linear regression to assess factors related to PAI-1 level.ResultsForty-six subjects with mean age 57 (IQR 53–62) years and Model for Endstage Liver Disease (MELD) score of 34 (IQR 30–40) were enrolled. Baseline characteristics were similar between NASH (n=10) and non-NASH (n=36) subjects except for rates of diabetes and hyperlipidaemia. Mean PAI-1 level was greater in NASH (53.9, 95% CI 33.3 to 74.5 mg/mL) when compared with non-NASH (36.1, 95% CI 28.7 to 43.5), p=0.040. NASH remained independently predictive of PAI-1 level prior to transplant on adjusted multivariable modelling (β 40.13, 95% CI 14.41 to 65.86, p=0.003). Conclusions: PAI-1 level is significantly elevated in decompensated NASH cirrhosis independent of other pro-haemostatic factors. This may explain the greater rates of venous thromboembolism in decompensated NASH cirrhosis. Future study focusing on prevention of venous thromboembolism in this population is paramount to improve patient-oriented outcomes given the high morbidity and mortality of venous thromboembolism and the significant impact it has on transplant candidacy.

show abstract

Section: Discussionmentioning

confidence: 93%

Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis

Rivas

Hummer-Bair

Bezinover

et al. 2021

BMJ Open Gastroenterol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite decades of research, NAFLD remains a complex, progressive disease process with many different pathogenic mechanisms and inputs. 12 Regular physical activity, in particular moderate-intensity aerobic exercise training, 13 can impact several pathogenic factors and may also influence gene expression. 14 , 15 While the mechanisms by which physical activity benefits patients with NAFLD remain poorly understood and understudied in patients, 16 , 17 regular physical activity, including exercise training, can lead to significant adaptations in not only the liver, but also in skeletal muscle and adipose tissue, each of which communicate with the liver through myokines and adipocytokines (Figure 1 ), and also the cardiovascular system.…”

Section: Pathogenesis Of Nafld and Mechanisms Explaining The Benefit ...mentioning

confidence: 99%

“… 23 Patients with NAFLD have significant dysbiosis with an overabundance of Gram-negative bacteria, which can lead to gut barrier dysfunction and a “leaky gut.” 24 , 25 After as little as 20 weeks of moderate-intensity aerobic exercise training, many beneficial effects have been observed on the gut-liver-axis in patients with NAFLD, including reversal of dysbiosis with the restoration of healthy bacterial balance as well as improvements in alpha (species richness) and beta diversity (species diversity). 13 , 23 Moreover, aerobic exercise training impacts bacterial gene expression in a way that may remove many of the pathogenic factors implicated in the development of NAFLD (Figure 1 ). 13 , 23 …”

Section: Pathogenesis Of Nafld and Mechanisms Explaining The Benefit ...mentioning

confidence: 99%

See 1 more Smart Citation

American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable report on physical activity and nonalcoholic fatty liver disease

Stine

Long

Corey

et al. 2023

Hepatology Communications

Self Cite

View full text Add to dashboard Cite

Background and Aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD. Approach and Results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.

show abstract

“…[111][112][113] Finally, exercise can modulate the gut microbiota towards a less steatogenic and insulin sensitizer phenotype. Indeed, in humans, exercise is associated with an increase in microbial richness/diversity, 114,115 an increase in the relative proportion of Bacteroidetes and Euryarchaeota, whereas a decrease in Actinobacteria, at the phylum level. 116,117 Obesity and MAFLD are known to be associated with a decrease in the Bacteroidetes/ Firmicutes ratio, which is associated with higher efficiency in harvesting energy from the diet.…”

Section: Physiopathology Of Exercise and Mafldmentioning

confidence: 99%

Aerobic Exercise in the Management of Metabolic Dysfunction Associated Fatty Liver Disease

Machado¹

2021

DMSO

View full text Add to dashboard Cite

Sedentarism is the pandemic of modern times. It is associated with several medical conditions including obesity, type 2 diabetes mellitus, cardiovascular diseases and also liver disease, particularly metabolic dysfunction associated fatty liver disease (MAFLD). In an era when MAFLD is the most prevalent chronic liver disease worldwide, whilst no pharmacological therapy has been approved for it, exercise has proved to be effective in improving liver steatosis. Interestingly, exercise decreases liver fat even in the absence of weight loss. The challenge for the clinician is to motivate the obese patient with MAFLD, and associated co-morbidities, who has crystallized a sedentary behavior, at times when every need is at the distance of a click on the Internet, and the entire world can be visited behind a screen. In this review, the aggregate evidence on the mechanisms and effects of exercise in the management of MAFLD is summarized, with simple recommendations for everyday clinical practice.

show abstract

Exercise Training Reverses Gut Dysbiosis in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis: A Proof of Concept Study

Cited by 14 publications

References 7 publications

Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis

Plasminogen activator inhibitor is significantly elevated in liver transplant recipients with decompensated NASH cirrhosis

American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable report on physical activity and nonalcoholic fatty liver disease

Aerobic Exercise in the Management of Metabolic Dysfunction Associated Fatty Liver Disease

Contact Info

Product

Resources

About