Nutrition has fashions and the most attractive
fashions are those that promise the most in terms of beneficial effects. An
important determinant of durability of a nutrition fashion is the challenges it
poses to experimental challenge. At present, the best example of a long living
nutrition fashion is the human gut microbiome which represents all of the
bacteria we house in our lower gut. Their main evolutionary basis was the
extraction of energy from food carbohydrates that are not amenable to digestion
by our digestive enzymes. However, in recent times these bacteria have been associated
with many diseases. If you get the wrong bacteria in your gut you increase the
risk of many diseases such as (non-exhaustive list: depression, anxiety,
autism, cancer of the lung and colorectum, pancreatitis, liver disease and many
gut disorders such as irritable bowel syndrome, Crohn’s disease and ulcerative
colitis. Of particular importance is infection of the gut with Clostridium
difficile which can be fatal in up to 30% of cases. Considerable success has
been achieved using faecal transplants of such patients with encapsulated bacteria
from a healthy donor.
Another condition which receives considerable
attention in relation to the gut microbiome is obesity The gut microflora of
obese persons differ from those with a normal weight and when obese persons
lose weight their gut microbe population moves in the direction of normal. But
the big question is cause and effect. Does an adverse microbiome population
cause obesity or does obesity cause an adverse microbiome population? In an
attempt to answer that question, a recent study examined the impact of faecal
transplantation of people with severe obesity (but who were metabolically
healthy, with no sign of type 2 diabetes, fatty liver or the metabolic syndrome)
with a capsule containing filtered faecal extract from a healthy normal weight female[1].
Twenty severely obese subjects (BMI 35+,Kg/M2) were randomly
assigned to either the treatment arm (encapsulated faecal transplant) or a
placebo arm (similar capsules with glycerol and colouring matter). The
treatment arm began with a booster level of transplantation which was then
followed by a reduced maintenance dose. They were told to eat normally and were
closely monitored throughout the 12 week treatment period. Probiotics were not
permitted for the study duration and for 4 weeks prior to treatment. Antibiotic
treatment was not permitted for 8 weeks prior to the treatment and then
throughout the treatment.
The obese patients did not lose weight. So, if
the microbiome theory of obesity is correct, why not? The first question : “did
the faecal transplant alter the gut microbiome composition’? And the answer is ‘yes,
it did’. Faecal samples were taken at several instances during the intervention
and the gut microbiome quickly resembled that of the healthy lean donor and that
was sustained throughout the study. The gut-microbiome theory also states that
the underlying effect is a change in the type of bile acids secreted with less
taurocholic acid type bile in faeces. So did the faecal transplant cause a
reduction of faecal taurocholic acid? Again, yes it did. And finally, central
to the obesity-gut microbiome theory is that the obese type is that the obesity
type microbiota alters the production of a gut hormone which plays a role in
weight regulation, the hormone glucagon-like peptide (GLP). Did the change with
treatment? No it didn’t.
Now, just as one swallow never made a summer,
one experiment never copper fastened a scientific theory. But it opens the
debate. It challenges the theory and that is what drives scientific enquiry.
Flaws can be found in this study and the authors list a few. Maybe it wasn’t
long enough for weight loss to occur. Maybe, but I doubt it since weight loss can
rapidly respond to treatment. Maybe the faecal transplant dose wasn’t strong enough.
Maybe, but I doubt this also, since the dose in use in the study changed the
composition of the microbiota.
So I’m left with the view that more studies
like this need to be completed to properly address this question. But let me
leave you with my final thought. Obesity is a consequence of overeating and the
caloric balance theory of obesity is to the microbiome theory what the Mona
Lisa is to graffiti. To paraphrase Bill Clinton: It’s the calories, stupid.
[1] Allegretti J et al
(2019) Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese
Patients. Clinical Gastroenterology and Hepatology (In press, available online)
