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Microbiome & Disease

A Letter from Liver


Pratibha

Feb. 22, 2019

Hi, I am your happy happy liver.

I am the filter of your body. I filter and detox your body from harmful substances that come in and allow only those which are needed. So, I am pretty important to you.

Specifically, I am a major filter of nutrients absorbed by the intestines and I am also the filter of microbiota generated by-products, filtering in the beneficial ones and filtering out the deleterious ones. Me, I am exposed (read bombarded) with these bacterial components and metabolites on a regular basis. One of the perks (or perils) of being so close to the intestine.

I have a two-way or cyclical connection with the gut, and in context, specifically with its microbiota.

Me and the intestine communicate extensively through the biliary tract, portal vein and systemic mediators. So, as I said, this begins with intestine passing on the digested metabolites and toxins to me and I filter in or filter out. For instance, some components of gut microbiota called Pathogen Associated Molecular Patterns (PAMPs) and Microbial Associated Molecular Patterns (MAMPs) needs to constantly filtered in or out. Some of these are endotoxins (lipopolysaccharide or LPS) that are deleterious and hence filtered out, and some are bacterial metabolites (examples) that are beneficial, hence filtered in. On the other hand, many intestinal factors regulating the bile acid production, glucose and lipid metabolism in ‘yours truly’ (liver). And… the cycle continues with my (liver) products, such as, influencing the gut microbiota composition, intestinal integrity and much more.

Things get messy when the gut microbiome dysbiosis happens (as in variation in gut microbiome composition and abundance), along with multiple interactions with human’s immune system and other cell types. This dysbiosis can cause imbalance in our otherwise harmonious communications, which in turn can have some deleterious effects on me (Well… just like any other relationship).

So what does the relationship counsellor say..?

They say there is some research that have already reported and much research going on linking my disorders and conditions to gut microbiota. It is now widely accepted that the damage caused to me (liver) can result from extensive interplay between the gut microbiota produced specialized molecules (such as TMA, acetaldehyde and LPS) and the host immune system, via Kupffer-cell-mediated liver inflammation.

I know, I know
This is too technical
But, let me explain what I have understood, taking an example.

Incidence of Non-alcoholic fatty liver (NAFLD) is globally rising and it is a common multi factorial liver disease. This is the condition where, I become inflamed and huge, scarred and scaled, and I don’t like myself like this.

How is this caused?
Remember the endotoxins? the deleterious things I filter out?

Some initial disruption of the intestinal integrity increases the permeability of its walls that leads to increased bacterial translocation, which in turn increased that load of bacterial endotoxins that penetrate the portal vein (more than I can handle). These endotoxins are recognized by toll-like receptors (TLRs) on hepatocytes (my cells). When bacterial LPS signals through TLR4, signalling ultimately activates NF-κB and proinflammatory cytokines, and initiate a barrage of immunologic responses. Together, this increases the risk of NAFLD development through the activation of hepatic inflammatory cells (that’s me!).

So, intestine is the cause
Why are u still in this relationship then?

Well… as it almost always happens in a relationship, when one door closes, another opens. What seems to be cause for my demise, the gut microbiota, is in itself the cure.

Firstly, increasing reports of links between NAFLD and gut microbiome, both at observational and at mechanistic levels, have indicated them as an attractive source of biomarkers for early diagnosis of NAFLD.

So, the microbiota that cause my disease, are also used to identify if I will get the disease.
That’s a good thing.
In fact, serval gut microbiome-based tests are already available, which can understand what your BugSpeaks® about your health and provide you with risk estimations of diseases that you may be predisposed to. This can be used later to confirm the findings with physicians and clinicians, and even get personalized recommendations.

Now to the cure or alleviation or protection of my disease

A major beneficial role of the gut microbiota in liver disorders is also supported by accumulating evidences that several complications of severe liver disease, such as hepatic encephalopathy, are efficiently treated by various prebiotics and probiotics. Gut microbiota manipulation through nutritional factors, with prebiotic potential, with additive probiotics, and supplementary polyphenols can alleviate the characteristics of NAFLD.

Of these, dietary factors are strong predictors of the gut microbiota composition. In fact, it has been projected that dietary factors play a more important role in shaping the gut microbiota composition than do genetic factors. Nutritional factors and the gut microbiota have bilateral interactions that contribute to the development and/or protection from NAFLD.

Most importantly, gut microbiota using prebiotic and fermentable carbohydrates as energy sources, have major beneficial impact on NFALD. Short Chain Fatty Acids (SCFAs), such as propionate, produced through this fermentation, cross the gut barrier and reach the liver through the portal vein blood. Propionate inhibits lipogenesis by acting on the transcription of several rate-limiting enzymes involved in de novo lipogenesis. Consequently, these fibres and their metabolites are putative tools to reduce steatosis and inflammation.

Hence, I am saved. Phew!!

Pratibha

Feb. 22, 2019