Obesity-induced gut microbiota dysbiosis can be ameliorated by fecal microbiota transplantation: a multiomics approach

Abstract

2 18 Abstract 19 Obesity and its comorbidities are currently considered an epidemic, and the involved 20 pathophysiology is well studied. Recently, the gut microbiota has emerged as a new potential 21 therapeutic target for the treatment of obesity. Diet and antibiotics are known to play crucial 22 roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the 23 manipulation of gut microbiota may represent a strategy for obesity treatment. Fecal microbiota 24 transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese 25 subject, has aroused interest as an effective approach for the treatment of obesity. To determine 26 its success, a multiomics approach was used that combined metagenomics and metaproteomics 27 to study microbiota composition and function.28 To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the 29 gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before 30 fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our 31 results showed that a high-fat diet induces changes in microbiota biodiversity and alters its 32 function in the host. Moreover, we found that antibiotics depleted the microbiota enough to 33 reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as 34 an obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the 35 microbiota balance, which restored normal functioning and alleviated microbiota disruption.38 Obesity is defined as a disequilibrium in energy balance and is currently a global health problem 39 in Western societies, where its prevalence has increased considerably in recent years. Obesity 40 triggers a vast number of comorbidities associated with hypertension, cardiovascular disease, 41 and diabetes, as well as other conditions [1]. It is widely known that obesity is affected by 42 numerous factors, such as diet, lifestyle and genetic background [2], and recently it has been 43 shown to be related to gut microbiota [3], which have been implicated in energy homeostasis 44 and metabolic functions [4]. Moreover, the same factors that affect obesity can modulate gut 45 microbiota composition, and the function of the gut microbiota will be affected by factors 46 involved in gut microbiota-host equilibrium [5].47 Several diet-induced animal models of obesity can be used to explore the mechanisms involved 48 in obesity. There are different obesogenic diets that can be employed. One example of these 49 diets is the semi-purified high-fat diet [6,7]. These types of diets are more commonly used in 50 these models due to their well-defined nutritional composition [8][9][10].51 Alterations in the gut microbiota composition have been shown to result in an imbalance that 52 leads to dysbiosis, which likely will have dramatic effects on the maintenance of health [11].53 Fecal microbiota transplantation (FMT) is a new and stra...

TMAO: how gut microbiota contributes to heart failure

“…Currently, FMT has been clinically shown to be effective for treating intestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease. 121 Some parenteral diseases are also being explored, such as autism, 122 obesity, 123 and type 2 diabetes. 124 Vrieze et al 125 performed FMT treatment on patients with metabolic syndrome, and the result indicated that patients receiving gut flora from leptin donor displayed improved insulin sensitivity and increased butyrate production.…”

Transfer with microbiota from lean donors prevents excessive weight gain and restores gut-brain vagal signaling in obese rats maintained on a high fat diet

“…In the current study, we sought to understand whether normalizing gut microbiota composition in HF fed obese animals would offset the detrimental physiological effects of consuming an energy dense, high in fat and sugar, diet. Prior reports (40,55), have shown that preventing dysbiosis in HF fed animals improves metabolic outcomes. Most of these interventions were started at the same time as HF diet introduction.…”

Characterizing conjugative plasmids from an antibiotic-resistant dataset for use as broad-host delivery vectors

“…Recent advances in our knowledge of host-associated microbiomes have made it clear that these communities are crucial to maintain their host's health. Changes in the community structure of a microbiome can result in a disease-associated state known as "dysbiosis" (Guirro et al, 2019;Sobhani et al, 2019;Tanja Dapa et al, 2022). It has also been shown that some human gut commensal bacteria perform deleterious functions, contributing to disease (Rath et al, 2018).…”

“…This strategy provides a targeted approach, resulting in species-or gene-specific manipulation, which can lead to detectable mechanistic and ecological effects. This lies in contrast to broad methods of microbiome manipulation, such as the use of prebiotics (Enam and Mansell, 2019), use of probiotics (Mao et al, 2018), and fecal microbiota transplant (FMT) (Guirro et al, 2019), which produce global effects in the community whose outcomes might be hard to predict. Additionally, since plasmid transfer has been observed across phyla (Klümper et al, 2015) and even across domains (Bates et al, 1998), conjugation has the potential to deliver DNA to a wide variety of hosts.…”