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The contribution of the gut microbiome to bariatric surgery

The gut microbiome has been identified as a potential factor in weight regulation. Thirty-nine percent of the adults are overweight (25–۲۹.۹ kg/m2) and 13% are obese (BMI≥۳۰kg/m2) worldwide. Recently, it has been found that obesity may affect brain function and structure, as it is associated with impaired cognition and alterations in gray matter (GM) and white matter (WM). Moreover, a higher BMI and waist-to-hip ratio (WHR) have been associated with lower fractional anisotropy (FA) values. Moreover, it is proposed that obesity increases the risk of developing dementia later in life by 60–۹۰%, versus healthy weight individuals. A growing of evidence reveals that obesity is related with alterations in neuroendocrine production and secretion, including ghrelin, insulin, GLP-1 and PYY.

Bariatric surgery for obesity treatment

Bariatric surgery is an effective treatment for obesity leading to rapid and sustainable weight loss. Bariatric surgery decreases body weight not only due to physical effects such as reduced food intake and malabsorption but also due to the various neuroendocrine changes which affect energy homeostasis and hunger/satiety. Moreover, Bariatric surgery might improve the gut microbiota diversity and restore white adipose tissue function, which can improve obesity-related immunological and cognitive impairments. The gut-brain axis consists of a bidirectional communication system, connected through the vague nerve, spinal fibers and sympathetic and parasympathetic fibers which are directly innervating the gastrointestinal tract. These elements communicate through endocrine messengers, neuro-immune mediators and neuroactive metabolites.

Conclusion

To summarize, Bariatric surgery is a good procedure to treat obesity and its related pathologies, however long-term effects remain unsolved. Future research should focus on the long-term effects of Bariatric surgery, to be able to investigate the neuroendocrine, microbiota and white adipose tissue changes and to potentially determine the new “normal” after homeostatic adjustments. Various studies have focused on neuroendocrine alterations already after six months. Six months post-surgery patients lose weight rapidly and generally still follow their post-operative diet. Therefore, the observed effects 6 months post-surgery might differ at longer follow-ups, when patients achieve a stable weight, or regain weight.

References

Provided by: Dr. Nazila Kassaian

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Gut Microbiome Varies Hour to Hour, Month to Month

The researchers in CHICAGO found that composition of a person’s intestinal microbial population differs from morning to night and from one month to the next. This individual shifts over time may explain why drugs don’t work the same in everyone.

Analysis of more than 18,000 timestamped stool samples collected worldwide indicated that centered log-ratio values (a measure of relative abundance) for different bacterial phyla and families commonly found in the gut microbiome varied substantially over the course of a single day, and also over a full year, according to senior investigator Amir Zarrinpar, MD, PhD, of the University of California San Diego.

Populations of some phyla, such as Actinobacteriota, tended to peak in the afternoon and evening. Others, such as Proteobacteria, were more abundant in the morning, with troughs later in the day.

Thus, at one point in the day certain types of bacteria may predominate but a wholly different composition may appear a few hours later. More than a third of phyla analyzed showed some degree of diurnal cycling after adjusting for confounding variables.

Similar patterns were seen across seasons: Proteobacteria hit their annual zenith in the summer and a winter trough, while a massive peak was found for Bacteroidota in late autumn and a nadir in late spring. The time plot for Verrucomicrobiota showed a double peak, in spring and again in the fall at a similar level.

Seasonal variations in temperature, humidity, and other environmental factors, likely drive these changes, with different types of bacteria responding in their own peculiar ways.

With regard to diurnal cycling, such influences are cited as “nutrient and water availability and sleep” as important factors.

 These previously unsuspected shifts in gut bacteria might help explain why all people don’t respond to a particular drug in the same way, insofar as the microbiome is important in metabolizing them and can affect organ function in other ways as well.

The scientists always wonder why certain patients respond more robustly to some medications than others. In terms of performing clinical trials, especially if it’s a wide-ranging and multiyear study, it’s important to remember that perhaps there may be seasonal variations in response to a drug, and if so, it may be affected by something like the relationship of the microbiome, the host immune system, or post-metabolic processes.

The data show some regional and ethnic differences in the diurnal cycling patterns.

It is indicated that an important direction for future research is to examine whether the diurnal and seasonal variations correlate with individuals’ health status.

Prepared by: Nazila Kassaian

Reference

by John Gever, Contributing Writer, MedPage May 4, 2023

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The link between chronic fatigue syndrome and the gut microbiome

chronic fatigue syndrome

Chronic fatigue syndrome (CFS), otherwise known as myalgic encephalomyelitis (ME), characterized by excessive fatigue that can’t be attributed to an underlying medical condition. People with the condition may experience symptoms ranging from headaches, memory and cognitive problems, and unexplained pain to digestive disturbances. It gets worse with physical or mental activity, and doesn’t get better with rest. The patients who have chronic fatigue syndrome complain for these symptoms: Continually in pain, Always tired, Unable to maintain a normal career and relationships.

Most of individuals with ME/CFS say a huge challenge is getting the condition diagnosed—a process that involves ruling out a host of other health problems. In medical research, a biomarker of this condition has so far been elusive.

The Role of Gut Microbiota in ME/CFS

Recent studies has been focused on identifying a biological parameter for diagnosing chronic fatigue syndrome through gut microbiota.

Now, a promising line of research is exploring whether a biomarker for ME/CFS might be found in the gut microbiota. These days, scientists inching closer to the urgently needed biological parameter that would aid diagnosis of this mystifying disease.

The scientists from Columbia University in 2017, compared a group of people with ME/CFS with healthy individuals. Some in the ME/CFS group also had a diagnosis of irritable bowel syndrome (IBS).

Circulating immune cells did not end up distinguishing between two groups. However, the gut microbiota was different in them. A main finding from the study was that in people with ME/CFS who also had IB, gut microbiota wise, from those with ME/CFS without IBS. Increased Bacteroides abundance along with a specific decrease in the species Bacteroides vulgatus seemed to indicate ME/CFS without IBS.

The top biomarkers of ME/CFS with IBS were an increased abundance of Alistipes and decreased Faecali bacterium in the gut, compared to healthy controls.

Conclusion

Based on the bacterial profiles, researchers were able to predict the three different groups with impressive accuracy: people without ME/CFS, people with ME/CFS alone, and people with ME/CFS and IBS. In addition, researchers also found that the markers of ME/CFS in general, regardless of IBS, included a decrease in certain bacterial metabolic pathways in the gut. Researchers also found an intriguing correlation between the severity of certain symptoms (including pain, fatigue, and reduced motivation) and the abundance of various bacteria and metabolic pathways in the people with ME/CFS.

This study indicates that gut bacterial dysbiosis specific to ME/CFS could be difficult to separate from the dysbiosis typical of IBS. The investigators noted the interesting overlap between the two conditions: They emphasized: “Much like IBS, ME/CFS may involve a breakdown in the bidirectional communication between the brain and the gut mediated by bacteria, their metabolites, and the molecules they influence”

Summary

While the study ultimately doesn’t shed light on the underlying cause of ME/CFS, it provides evidence of gut microbiota dysbiosis in ME/CFS, along with hope for finding an eventual biomarker, most promisingly in gut microbiota composition or bacterial metabolic pathways. Research teams still have a long way to go, but the biomarker they hope to find will mark a turning point for patients with this mysterious disease.

References

Giloteaux L, Goodrich JK, Walters WA, et al. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2016; 4:30.

Nagy-Szakal D, Williams BL, Mishra N, et al. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2017; 5:44.

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?What is Paraprobiotic

Paraprobiotics or immobilized probiotics, are kind of postbiotics which when ingested, may have the ability to exert positive biological responses and restore intestinal homeostasis in a similar manner to probiotics. Paraprobiotics are currently being referred to as modified, inactivated, non-viable, para- or ghost probiotics. Paraprobiotics, the immobilized version of probiotics are gaining traction in recent years due to the concerns about the possibility of low tolerance of probiotics, especially in pediatric populations and in severely ill or immunocompromised patients.  Paraprobiotics seem to have similar beneficial properties as live probiotics with fewer of the constraints associated with unstable, diminishing bacteria.

Production of paraprobiotics

Paraprobiotics could be generated using different methods including: Heat-inactivation, Ultraviolet-inactivation, Chemical treatment (e.g. formalin), Gamma-irradiation, and Sonication. In most cases, heat treatment is considered the method of choice for deactivating probiotic strains. The effect that different types of inactivation have on bacterial structure and components as well as the maintenance of probiotic properties requires further research.

Mechanism of action

The mechanisms of action for paraprobiotics is less understood, though the possible mechanisms include immune system regulation and interference with pathogen attachment to host cells. Limited research hypothesizes that immobilized paraprobiotics release key bacterial components, such as lipoteichoic acids, peptidoglycans, or exopolysaccharides which exhibit key immunomodulation effects and antagonizing properties against pathogens.

General paraprobiotics applications

 Emerging clinical and pre-clinical studies have demonstrated that paraprobiotics play a role in general health and well-being and for improving host immune function like that of probiotics. It is proved that paraprobiotics induce changes in the gut microbiome and the altered gut microbial composition is associated with increased levels of innate and acquired immunity biomarkers. Paraprobiotics also seem to exhibit antioxidant effects and has indicated its potential applications in food and pharmaceutical industries.

Paraprobiotics applications in clinical treatment

Paraprobiotics (mostly heat-killed) seem to be beneficial for the following clinical applications:

  • Gastrointestinal diseases; bloating, pediatric disorders, infantile colic, diarrhea, extra-intestinal diseases
  • Upper respiratory tract infections
  • Ocular disorders including eye fatigue
  • Asthma
  • Inflammatory bowel diseases (ulcerative colitis)
  • Colitis-associated colorectal cancer
  • Type 2 Diabetes (improved glycemic parameters)
  • Liver injury
  • Atopic dermatitis
  • Influenza viruses
  • Cardiac injury

Species used as paraprobiotics

Many species of bacteria have been identified to have benefits as paraprobiotic strains including:

Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Enterococcus faecalis,  Lactobacillus acidophilus, , Lactobacillus bulgaricus, Lactobacillus casei , Lactobacillus delbrueckii subsp. Bulgaricus, Lactobacillus fermentum, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri , Lactobacillus salivarius, Lactococcus lactis , Streptococcus salivarius  and subsp. thermophilus.

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Gut microbiome changes in non-alcoholic fatty liver disease & alcoholic liver disease

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are some of the most common liver diseases worldwide. The human gut microbiome is dynamic and shifts in bacterial composition have been implicated in many diseases. Studies have shown that there is a shift in bacterial overgrowth favoring pro-inflammatory mediators in patients with advanced disease progression such as cirrhosis. Further investigation demonstrated that the transplantation of gut microbiota from advanced liver disease patients can reproduce severe liver inflammation and injury in mice. Various techniques in manipulating the gut microbiota have been attempted including fecal transplantation and probiotics. This review focuses on the changes in the gut microbiota as well as emerging lines of microbiome work with respect to NAFLD and ALD.

General challenges in conducting and interpreting microbiome studies and its implications for NAFLD and ALD

 Despite technical advances in the rapidly evolving field of microbiome research, the reproducibility and validity of findings deserve special attention. Large data sets with several competing variables often confound the observations compared to a rather clean disease state in an experimental model. In addition, complex ecosystem of host, genetics, and environmental factors such as the mode of delivery, diet, alcohol, medications, antibiotic use, etc. can cause variations in the composition as well as functionality of the gut microbiome. Another important but often overlooked technical aspect in human microbiome studies is the collection, processing and handling of the bio specimens and the use of different sequencing methods, which yield different results. Therefore, designing future studies in liver disease research should focus on overcoming some of these challenges to produce more robust, reproducible, generalizable and clinically applicable data at an individual and population level.

Reference

Kwong EK, Puri P. Gut microbiome changes in Nonalcoholic fatty liver disease & alcoholic liver disease. Translational Gastroenterology and Hepatology. ۲۰۲۱; ۶.