Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health

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Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
Report
9th edition - 2020
Moving gut microbiome science
from the bench to actionable advice:
major learnings and paths to explore

Madrid (SPAIN)
Gut microbiome science has exponentially increased over the last two decades,
as has the general population’s interest in harnessing this knowledge for
better health. When it comes to science-backed tools for improving our gut
microbiome, according to experts’ conclusions from the GMFH World Summit
2020, diet diversity, prebiotics and probiotics are all worth considering.

Sponsoring societies                Endorsing societies   The 2020 summit has been made
                                                          possible by our major supporters:

                                                          Biocodex, Danone (the Founding
                                                          Supporter) and Sanofi.
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
ADVANCING GUT MICROBIOME SCIENCE
   FOR BETTER HEALTH IS NOT STRAIGHTFORWARD:
                   THE MAJOR CHALLENGES
                 AND HOW TO OVERCOME THEM

Gut microbiome publications have        •T
                                         aking into account individuality
exponentially increased over the         when interpreting microbiome
last decade, with the subsequent         studies;
impact on both basic science re­
                                        •A
                                          voiding defining a gut micro­
search and clinical practice. While
                                         biome as ‘healthy’ or ‘unhealthy’
it is clear that the roadmap to cli­
                                         (any effect of the gut microbiota
nical translation consists of deve­
                                         on host health is likely to depend        “The microbiome
loping gut microbiome-related so­
                                         also on individual host genetics,         will prove to be
lutions for better health, Colin Hill
                                         diet and environment);                    a rich source of
from University College Cork (Cork,
Ireland) acknowledged during his        • Considering all factors that can sha­   therapies and
keynote lecture that higher stan­          pe gut microbiota composition;
                                                                                   smart food, feed
dards must be rigorously applied to     •C
                                          hoosing the right methodology
overcome roadblocks when moving                                                    ingredients and diets
                                         for studying the gut microbiome;
from bench to bedside.                   and                                       that will improve the
                                        •H
                                          aving long-term data regarding
                                                                                   human condition.”
To deliver precision gut microbiome-     the safety of gut microbiota-tar­         Colin Hill
based science, accuracy (and a           geted interventions n
healthy dose of common sense) is
necessary in all steps: from micro-
biome sampling to specific lan­
guage used when explaining the
benefits of taking care of the gut
microbiota. Hill explained that ma­
jor challenges to be addressed to
get the right microbiome science
include:
•U
 sing precise language when
 communicating gut microbiome
 science;
•
 Adopting consensus definitions
 (see the ISAPP consensus docu­
 ments of probiotics and prebio­
 tics);
•R
  elying more on actual numbers
 rather than percentages when
 clarifying to what extent two or
                                                                                                          ©D.R.

 more microbiomes are identical
 or different;

                                                                                                Report 2019
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
WHICH HOST AND DIET FACTORS
SHAPE THE GUT MICROBIOME?

Each person has the gut                   of a C-section on the infant’s gut      Rectal mother-to-
                                          microbiome is barely noticeable du­
microbiome they deserve                   ring the first weeks of life and when   child transmission,
and this is how it changes                the procedure is performed (that        rather than vaginal
throughout life                           is, before or during labor) affects     bacteria, appears
                                          children’s gut microbiome in the
                                          same way. In this regard, the high
                                                                                  to affect newborn
The first three years of life represent   number of shared strains between        gut colonization
the most critical period for dietary      C-sections and vaginal deliveries       efficiency.
interventions aimed at gut micro­         suggests that rectal mother-to-
biota modulation to improve child         child transmission, rather than va-
growth and development and posi­          ginal bacteria, appear to be what
tively affect health. Moran Yassour       affects newborn gut colonization
from the Hebrew University of Jeru­       efficiency.
salem (Israel) focused on the origin
and extent of microbe transmission
from mother to infant. A longitudi­
nal sampling of gut bacterial trans­
mission in 44 mother-infant pairs
enabled Yassour and colleagues to
find that two patterns of mother-
to-child bacterial transmission exist
in the first 3 months of a child’s
life. While often the mother’s do-
minant strain (Bacteroides vulga-
tus and Bifidobacterium adoles-
centis) is transmitted to the child,
sometimes her secondary strains
(often Bacteroides dorei) can pre-
ferentially colonize the infant gut.
Interestingly, in families where the
secondary strain of Bacteroides uni-
formis is inherited, a starch utiliza­
tion gene that is missing in the mo­
ther is available in the newborn for
facilitating the metabolism of the
mother’s milk, explained Yassour.
                                                                                  Diet keeps the gut
Likewise, the transmission of some        Paul O’Toole from University Colle­
antibiotic resistance genes may also      ge Cork (Ireland) covered diet-mi­      microbiome fit in the
be inherited.                             crobiota health interactions in el­     elderly: it is not the
                                          derly people (aged >65 years). In       quantity of calories
Regarding the impact of delivery          this population, lifestyle and habi­
mode on the child gut microbiome,         tual diet can outweigh age-related      per se that matters,
Yassour explained that, contra­           gut microbiota changes. Specifi­        but the quality
ry to common belief, the impact           cally, elderly people living in their   of the diet.

                                                                                            Report 2020 - 3
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
homes and looked after by care­          correlated with inflammation, in a
givers show the highest diversity        manner independent of body mass
in their gut microbiota, with sub­       index and age. It was also possible
jects residing in long-term care         to identify 44 Operational Taxono­
facilities (consuming a diet with a      mic Units (OTUs) that were more
low diversity of food components)        abundant when the MedDiet was            “Our findings
showing the least diverse microbio­      strictly observed (named “diet posi­     show the benefits
ta. Furthermore, these microbiota        tive”), whereas 45 OTUs were nega­
changes correlated with increased        tively associated with adherence to
                                                                                  of following a
frailty and increased values of mar­     the diet (named “diet negative”). In     Mediterranean diet
kers of inflammation, explained          conclusion, the study supports the       to modulate the gut
O’Toole.                                 fact that diet quality matters more      microbiota, which,
                                         than the quantity of calories per se,
                                                                                  in turn, has the
The gut microbiota composition           even in subjects of advanced age,
profile groups change according to       and gut microbiota can explain the       potential to promote
the duration of stays in long-term       benefits of a highly diverse and ba­     healthier aging.”
residential care and O’Toole’s re­       lanced diet.                             Paul O’Toole
search group was interested in ex­
ploring whether modulation of the
gut microbiota through diet could
lead to healthier aging. A dietary
intervention in elderly subjects and
young healthy controls showed
how an intake of prebiotics with a
high content of resistant starch for
6 months can modulate specific
gut microbiota taxa (such as Ru-
minococcaceae, Parabacteroides,
and Phascolarctobacterium) and
reduce inflammation in the elder­
ly. In the light of these findings, it
might be possible to improve the
loss of certain taxa in the gut mi-
crobiota of frail long-stay older
people through prebiotic supple-
mentation.

In another study presented, O’Toole
and colleagues showed that adhe-         Your allies for looking
rence to the Mediterranean diet
(MedDiet) for 1 year in 612 elder-       after your gut microbiota:              Not all fermented foods are
ly non-frail and pre-frail European      fermented foods,                        a source of probiotics. Learn
subjects led to a higher abun-           probiotics and prebiotics               more about the impact of
dance of different taxa that are                                                 kefir and major non-dairy
positively associated with markers                                               fermented foods on the gut
of lower frailty and better cogni-       Different dietary strategies are cur­   microbiota and gastrointesti-
                                                                                 nal health here.
tive function but also negatively        rently undergoing a surge in po­

                                                                                                 Report 2020 - 4
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
“The most widely
                                                                                  investigated
                                                                                  fermented foods are
                                                                                  fermented milks
                                                                                  and kefir, with
                                                                                  human evidence
                                                                                  suggesting beneficial
                                                                                  effects on lactose
                                                                                  malabsorption
                                                                                  for yogurt and
                                                                                  functional
                                                                                  constipation, lactose
pularity, as a means of improving       bacteria and yeast within the gas­
gastrointestinal health by shaping      trointestinal tract. However, Whelan      malabsorption and
the gut microbiota. Kevin Whelan        acknowledged that not all probio­         Helicobacter pylori
from King’s College London (United      tics work in the same way and ca­         eradication for kefir”
Kingdom) summarized human in­           reless use of this word as a generic      Kevin Whelan
tervention studies investigating the    descriptor without specifying the
impact of fermented foods, probio­      content (genus, species and strain)
tics and prebiotics on gastrointesti­   or clinical indication often makes for
nal health and disease. The most wi-    a superficial imprecise term. In addi­
dely investigated fermented foods       tion, humans’ response to probiotics
are fermented milks and kefir, with     is highly individualized and clini-
human evidence suggesting be-           cians should focus on health outco-
neficial effects on lactose malab-      mes rather than whether a probiotic
sorption for yogurt and functional      colonizes or has detectable effects
constipation, lactose malabsorp-        on the indigenous microbiota. Pro­
tion and Helicobacter pylori era-       biotics have been shown to be bene­
dication for kefir. There is limited    ficial in constipation, irritable bowel
clinical evidence for the effective­    syndrome (IBS) and ulcerative coli­
ness of kombucha, sauerkraut, soya      tis, whereas their role in Crohn’s di­
fermented foods (miso, natto and        sease is controversial.
tempeh), kimchi and sourdough in
gastrointestinal health and disease,    Prebiotics, meanwhile, act by se­
explained by a variable microbial       lectively stimulating the growth
composition in fermented foods          of some gut bacteria. The most
and the lack of human studies.          studied prebiotics are inulin-type
                                        fructans (inulin, oligofructose) and
Beyond fermented foods, probiotics      galactooligosacharides, while resis­
are also a way to deliver beneficial    tant starch and pectins are conside­

                                                                                                 Report 2020 - 5
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
Physicians Committee for Res­
                                                 ponsible Medicine (USA) presented
                                                 the results of a randomized clinical
                                                 trial looking at changes in gut mi­
                                                 crobiota in response to a low-fat
                                                 vegan diet. In 147 parti­cipants who      “Our study
                                                 were overweight and insulin resis­        highlights the
                                                 tant but who had not yet been dia­        importance of fiber
                                                 gnosed with diabetes, Kahleova and
                                                 colleagues looked at their fecal mi­      intake for diabetes
                                                 crobiota, body composition and in­        prevention because
                                                 sulin sensitivity at baseline and after   Faecalibacterium
                                                 randomizing them to follow a vegan
                                                 diet or to stay on their usual diet for
                                                                                           prausnitzii feed on
                                                 16 weeks.                                 fiber and produce
                                                                                           short-chain fatty
                                                 The vegan diet led to a 5.8kg re­
                                                                                           acids with positive
Adobe Stock

                                                 duction in body weight, which was
                                                 mainly due to a reduction in fat mass     metabolic benefits.”
          The vegan diet.                        analyzed using dual energy X-ray          Hana Kahleova
                                                 absorptiometry. More interestingly,
         red candidate prebiotics. Similar to    metabolic outcome improvements
         what happens with probiotics, Whe­      were also related to changes in the
         lan explained that the response to a    gut microbiome. Specifically, an in­
         prebiotic is largely affected by the    crease in the butyrate-producing
         background gut microbiota profile       bacterium Faecalibacterium praus-
         and habitual dietary fiber intake.      nitzii – which has been found to be
         Science-backed indications for pre­     depleted in patients with type 2 dia­
         biotics include constipation and IBS.   betes and has also been linked to in­
                                                 creased inflammation and increased
                                                 insulin resistance – in response to
         A 16-week plant-based                   the vegan diet was associated with
                                                 changes in body weight, fat mass
         diet can boost the gut                  and visceral fat. In addition, the ve­
         microbiome, helping with                gan diet led to less of a drop in Bac­
         weight loss and overall                 teroides fragilis compared with the
                                                 Western diet, and that too was re­
         health                                  lated to changes in weight loss, fat
                                                 mass and insulin sensitivity n
         A wealth of data has shown the be­
         nefits of plant-based diets for pre­
         venting and managing diabetes,
         with gut microbiome research
         con­necting the dots between in­
         flammation, insulin resistance and
         diabetes. Hana Kahleova from the

                                                                                                           Report 2020 - 6
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
THE GUT MICROBIOME-IMMUNE SYSTEM BALANCE:
WHY DOES IT MATTER?

The neonatal period
                                                     integrity, and even tryptophan and
spanning birth to                                    nucleotide metabolism in offspring.
weaning represents the                               “As the early-life microbiota is see-
most critical period for                             ded by vertical transmission, the
                                                     education of immunity in offspring               “As the early-
dietary interventions                                is critically dependent on mater-                life microbiota is
aimed at microbiota                                  nal commensals,” acknowledged
                                                                                                      seeded by vertical
modulation.                                          McCoy. In addition, the maternal
                                                     microbiome can also have an im­                  transmission,
                                                     pact on disease development la­                  the education
Kathy McCoy from the University of                   ter in life. It seems that an altered            of immunity
Calgary (Canada) covered the in­                     microbiota can increase intestinal
fluence of maternal gut microbiome                   permeability and thus promote the                in offspring is
on the training and maturation of                    development of a pro-inflammatory                critically dependent
the neonatal immune system, even                     milieu that stimulates beta-cell au­             on maternal
before birth. McCoy started by pro­                  toimmunity in the predisposed host.
viding evidence supporting the                       For example, differences in human
                                                                                                      commensals”
                                                                                                      Kathy McCoy
theory that seeding of early-life                    milk oligosaccharide-utilizing bac­
microbiota with maternal microbes                    teria provide a route to differences
leaves a lasting imprint on the offs­                in immune education that may pre­
pring. Studies in mice have covered                  dispose the body to immune and
the critical role of colonization by                 metabolic-related conditions such
maternal microbes in early life for                  as diabetes.
normal immune development, inclu­
ding innate immune cell production,                  Gérard Eberl from Institut Pasteur
antibody production, immune regu­                    (Paris, France) presented findings
latory functions, epithelial barrier                 in mice showing how important an

  Effects of the maternal microbiota on early life immune development           Time windows for immune development by microbiota.
  Source: McDonald B & McCoy KD, Science. 2019; 365(6457):984-5.                Source: Al Nabhani Z et al., Immunity. 2019; 50(5):1276-88.

                                                                                                                          Report 2020 - 7
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
adequate response by the immune             in terms of host genetic susceptibi­
system to the expanding gut micro­          lity is unknown. Sokol shared obser­
biota during the gradual switch from        vational data showing associations
a diet composed exclusively of milk         between four major genetic va­
to a diet that includes other foods         riants linked to an increased risk of
is for health later in life. However, an    IBD and gut bacterial populations.       “In order to develop
altered gut microbiota during the           Within them, a link between NOD2         a balanced immune
weaning period (e.g., secondary to          genes and a reduction in both the
antibiotics or due to a high fat diet)      Roseburia and Faecalibacterium
                                                                                     system, mice and
may hinder adequate development             prausnitzii genera was replicated in     humans need to
of host immune responses, which             three independent cohorts. Overall,      be exposed to
leads to increased susceptibility to        these findings show that the gut
immune-related diseases such as             microbiota might be a potential
                                                                                     microbiota during
allergy later in life. The right food in­   mechanism underlying the asso-           the neonatal period
take during this weaning period also        ciation between IBD and genetic          spanning birth
matters for a balanced activation of        variants. In addition, gut microbio­
                                                                                     to weaning”
the immune system. For example,             ta-derived metabolites are gaining
                                                                                     Gérard Eberl
compounds of dietary origin such            interest as potential targets for
as retinoic acid, whose metabolism          precision therapeutic modulation
is affected by the gut microbiota,          in IBD. Increased tryptophan me­
appear to shape the developing im­          tabolism has been associated with
mune system. By contrast, microbial         the activity of IBDs, generating aryl
exposure after weaning does not             hydrocarbon receptor agonists that
alter the development of immune             have a wealth of effects on mucosal
responses, highlighting the critical        immunity and homeostasis.
window of weaning for preventing
immunopathologies in adult life.            Finally, Sokol shared the findings
                                            of a recent randomized controlled
                                            trial as the first to evaluate the use
                                            of fecal microbiota transplantation
The gut microbiome                          in maintaining remission in Crohn’s
and the immune system                       patients. The authors found a hi­
in inflammatory bowel                       gher rate of steroid-free remission
                                            in Crohn’s patients treated with FMT
disease: what is the                        as well as improved lesions and in­
chicken and what                            flammatory markers. Although fur­
is the egg?                                 ther studies on larger patient po­
                                            pulations are needed, the results
                                                                                     Learn more about the contri-
                                            of this pilot trial are promising for    bution of gut microbiota-de-
Harry Sokol from Saint Antoine Hos­         the many patients suffering from         rived metabolites in IBD here.
pital (Paris, France) updated major         Crohn’s disease. n
learnings on using gut microbiota
as a therapeutic tool in inflammato­
ry bowel diseases (IBDs). Although
specific gut microbiome signatures
have been defined in IBDs, the role
of the microbiota in the onset of IBD

                                                                                                    Report 2020 - 8
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
FOOD INTOLERANCES AND FUNCTIONAL
GUT DISORDERS ARE CLOSELY CONNECTED:
WHY IT IS TIME TO FOCUS
ON THE SMALL INTESTINE?

Although the small intestine is a      rier dysfunction in the absence of
harsh environment for microorga­       mucosal damage. Interestingly, Lac­
nisms to thrive, its involvement in    tobacillus can degrade ATIs, leading
driving immune responses and di­       to a reduction in its pro-inflammato­
gesting macronutrients makes it        ry effects. These findings open the         “Understanding the
worthwhile to explore in the context   potential of gut microbiome-modu­           basics of bacterial-
of food sensitivities and entero­      lating strategies through gluten and        diet interactions will
pathies. Alberto Caminero from         ATI-degrading bacteria in patients
McMaster University (Hamilton,         with wheat-related disorders.
                                                                                   help us better treat
Canada) presented findings sug­                                                    patients with food
gesting the gut microbiota’s invol­    Purna Kashyap from Mayo Cli­                sensitivities and
vement in the processes underlying     nic (Rochester, USA) focused on
gluten or wheat sensitivity. Certain   the small intestinal microbiome in
                                                                                   enteropathies, such
small-intestinal bacteria, such as     functional gastrointestinal disor­          as celiac disease”
Pseudomonas, produce elastases         ders. Small intestinal bacterial over­      Alberto Caminero
that contribute to gluten degrada­     growth (SIBO) has been suggested
tion. However, in mice expressing      as a culprit of common functional
genes associated with coeliac di­      gastrointestinal symptoms, inclu­
sease (HLA-DQ8), bacterial elas­       ding IBS and intestinal bloating.
tase can synergize with gluten to      However, there is no gold standard
induce severe inflammation. Simi­      for diagnosing SIBO and Kashyap
                                                                                  Learn more about current re-
larly, non-gluten proteins present     showed that high-throughput se-
                                                                                  search on how changes in the
in wheat, such as α-amylase trypsin    quencing analysis of the duode-
                                                                                  gut microbiota play a role in
inhibitors (ATIs), can induce an in­   nal microbiome, rather than dia-           food sensitivities: here.
nate immune response, causing bar­     gnosing SIBO using the traditional

                                                                                Wheat components involved in
                                                                                increased intestinal inflammation in
                                                                                patients with celiac disease or other
                                                                                wheat-related disorders
                                                                                (e.g., non-celiac wheat sensitivity and
                                                                                irritable bowel syndrome).

                                                                                                        Report 2020 - 9
Report 9th edition - 2020 Moving gut microbiome science from the bench to actionable advice: Gut Microbiota for Health
“Small intestinal
                                                                                bacterial overgrowth
                                                                                (SIBO) has been
                                                                                suggested as a
                                                                                culprit of common
                                                                                functional
                                                                                gastrointestinal
                                                                                symptoms, including
                                                                                IBS and intestinal
                                                                                bloating.”

aspiration and culture of small in-     that resolved on resumption of the
testinal contents, correlates with      subjects’ habitual high-fiber diet.
functional symptoms in 126 indivi-      This means diet affects the small
duals who had various gastrointes-      intestinal microbiome and may be a
tinal symptoms. Indeed, asympto­        factor determining SIBO.
matic individuals commonly met
criteria for SIBO. In addition, meta­   Beyond dietary fiber, Kashyap
bolic pathways involved in metabo­      acknowledged that other dietary
lizing simple sugars were enriched      components and drugs may modu­
in symptomatic individuals, whe­        late the small intestinal microbiome.
reas complex carbohydrate degra­        For example, consumption of a high
                                                                                “It is time to move
dation pathways were decreased.         fat diet can profoundly alter the       away from SIBO for
These findings led the investigators    microbiota in the small intestine,      predicting functional
to hypothesize that dietary factors     which increases fat absorption in
                                                                                gastrointestinal
might be relevant to alterations        mice. Although the long-term im­
of the duodenal microbiome and          pact of these results in the clinical   symptoms and
prompted them to examine the ef­        setting remains to be seen, it turns    to focus on the
fect of fiber content in the diet on    out that it is time to move away from
                                                                                small intestinal
gastrointestinal symptoms and the       SIBO for predicting functional gas­
small intestinal microbiome in 16       trointestinal symptoms and to focus     microbiome as a
healthy individuals. Switching to       on the small intestinal microbiome      key protagonist
a low-fiber and high simple sugar       as a key protagonist in functional      in functional
diet for 7 days increased small in-     gastrointestinal symptoms n
testinal permeability and induced                                               gastrointestinal
IBS-type symptoms (such as bloa-                                                symptoms.”
ting and abdominal discomfort)

                                                                                        Report 2020 - 10
THE MICROBIOME CANNOT BE IGNORED
WHEN LOOKING AT HOW DRUGS
ACT IN THE BODY

It is not only antibiotics                             of enteric infections caused by a de­
that can have an impact                                creased colonization resistance for
                                                       Clostridioides difficile infection due
on our gut bacteria; a                                 to a reduction of stomach barrier           “Microbiome studies
quarter of drugs designed                              function; and altering gut microbio­        should be corrected
to act on human cells                                  ta functions (e.g., increased purine
                                                       deoxyribonucleoside degradation
                                                                                                   for medications use,
do too.                                                as a source of carbon in PPI users).        including proton
                                                       Notably, long-term effects tied to          pump inhibitors,
Medication, together with diet,                        chronic PPI consumption include an
stands out as a major environmental                    altered response to immune check­
                                                                                                   metformin, laxatives,
factor that influences gut microbio­                   point inhibitors in cancer and the          selective serotonin
ta composition. Rinse K. Weersma                       development of childhood obesity.           reuptake inhibitors
from the University of Groningen
                                                                                                   and antibiotics.”
(Netherlands) highlighted that the                     Meanwhile, Athanasios Typas from
                                                                                                   Rinse K. Weersma
identification of a causal impact of                   the European Molecular Biology La­
proton pump inhibitors (PPIs) and                      boratory (Heidelberg, Germany) fo­
the anti-diabetic drug metformin                       cused on the impact of non-antibio­
on the gut microbiome provides                         tic drugs on gut microbes. Typas’s
firm evidence of gut microbiome                        group found that nearly one quar-
perturbation by drugs other than                       ter of more than 1,000 commonly
antibiotics. PPIs have the potential                   used drugs had antibiotic effects,
to alter the gut microbiota by redu­                   which are reflected in side effects
cing acidity in the stomach that leads                 in humans. Drugs that have the
to an overrepresentation of oral mi­                   most profound effect include anti­
crobes in the gut; increasing the risk                 cancer drugs, antipsychotics and

    Different scenarios in which drug-gut microbiome interactions can occur:
    Source: Doestzada M et al., Protein Cell. 2018; 9(5):432-45. doi: 10.1007/s13238-018-0547-2.

                                                                                                               Report 2020 - 11
antihypertensive drugs. As specific      and respond to in vivo signals, such                       “Selective antidotes
therapeutic classes target not only      as in the healthy or diseased gut.                         are being developed
human cells but also gut microbes,       The unique abilities of living or-                         as a means of
this might imply the role of poly­       ganisms with the potential to im-
pharmacy as a strong driver of an­       prove how we care for patients in-
                                                                                                    stopping the impact
timicrobial resistance. Typas also       clude being able to integrate and                          of antibiotics and
showed that the detrimental effects      respond to new signals; accessing                          human-targeted
of antibiotics on the gut microbio­      parts of the body inaccessible to
ta are not limited to their ability to   standard technology; producing
                                                                                                    drugs on gut
stop the growth of gut microbes          and delivering biological thera-                           commensals,
and include collateral damage such       peutics directly to the site of di-                        while not affecting
as the lysis of gut commensals. In       sease; and showing a durable per-
                                                                                                    antibiotic effects on
this regard, experimental research       formance (lasting even longer than
has started exploring selective an­      6 months) within the gut.                                  pathogens.”
tidotes for avoiding the side ef­                                                                   Athanasios Typas
fects of wide-spectrum antibiotics       On the whole, the use of live, en-
on Gram-negative gut commen­             gineered probiotics represents a
sals, while retaining activity for pa­   new frontier in managing gut di-
thogens.                                 seases and as a novel mechanism
                                         for drug delivery. Major challenges
                                         include the availability of libraries
The next frontier in                     and conditions to be tested in or­
                                         der to better understand bacteria
medicine: harnessing                     behavior within the complex gut
living bacteria in our                   environment n
body as a non-invasive
way to detect and treat
disease

David Riglar from Imperial Colle­
ge London presented the poten­
tial of engineering living bacteria
in our body as non-invasive tools
for detecting and treating disease.
The Riglar lab uses a combination
of synthetic biology, imaging and
sequencing-based approaches to
better understand the function of
the gut and its microbiota during
health and disease. Riglar explored
the potential of living engineered
probiotics for probing and control­
ling the gut environment. For exa­
                                                                                                                                        ©iStock

mple, studies have shown engi­
neered gut bacteria can survive in
                                         The use of live, engineered probiotics represents a new frontier in managing gut
the mouse gut and sense, record          diseases and as a novel mechanism for drug delivery.

                                                                                                                     Report 2020 - 12
GUT MICROBES SHOW THE WAY
TOWARDS BETTER
MENTAL HEALTH

John F. Cryan from University Colle­    have an impact on the intestinal
ge Cork gave an overall glimpse of      microbiota and subsequent men­
the role of intestinal microbiota in    tal illnesses in the developing teen.
regulating the gut-brain axis across    In addition, as we age, changes in
lifespan. The role of the gut micro­    the gut microbiota and associated
biota in brain and behavior is sup­     increases in gut permeability, in­
ported by initial findings in which     flammation and arterial dysfunction
                                                                                 “Gut bacteria are
germ-free mice showed alterations       may be important mediators of im­        directly linked to
in neuron myelination and activity,     pairments in the behavioral, affec­      our mental health.
dendritic growth and even blood-        tive and cognitive functions seen in
brain-barrier permeability. In other    aging.
                                                                                 We have coined the
words, the brain does not develop                                                term psychobiotic for
appropriately without microbes.         Due to the close interaction             means of influencing
Mode of delivery is among the most      between gut microbiota and the
                                                                                 the microbiome
studied factor playing a pivotal role   brain, scientists have started ex­
in regulating early brain develop­      ploring means of influencing the         for mental health
ment, with enduring neurobeha­          gut microbiome for the benefit of        benefits, including
vioral effects. More interestingly,     mental health. While the term psy­       probiotics,
C-section-induced effects on beha­      chobiotic was introduced by Iri­
vior can be reversed by targeting       sh scientists in 2013 and originally     prebiotics, synbiotics
microbiota with probiotics, at least    referred to a subset of probiotics       and postbiotics.”
in animal models. As for later in       that could produce a health bene­        John Cryan
life, Cryan explored the gut micro­     fit in those with psychiatric illness,
biota’s influence on brain develop­     more recently, the definition of psy­
ment through adolescence, which         chobiotics has expanded to include
is a time of enormous developmen­       other means of influencing the
tal change. Cryan explained that        microbiome for mental health be­
gut microbiota undergoes a shift        nefits. Psychobiotics, therefore, can
in structure and balance during         include a range of substances that       “Psychobiotics,
adolescence and external sources        affect microbiota-gut-brain axis si­
                                                                                 therefore, can
of stress during this period may        gnaling, including probiotics, pre­
                                                                                 include a range
                                                                                 of substances that
                                                                                 affect microbiota-
                                                                                 gut-brain axis
                                                                                 signaling, including
                                                                                 probiotics,
                                                                                 prebiotics, synbiotics
                                                                                 and postbiotics.”

                                                                                              Report 2020 - 13
“Serotonin of
                                                                                               microbial origin
                                                                                               can have an
                                                                                               impact on host
                                                                                               functions, including
                                                                                               gastrointestinal
                                                                                               motility and platelet
                                                                                               function.”

 Ways of targeting the gut microbiome for mental health benefits.
 Source: Long-Smith et al., Annu Rev Pharmacol Toxicol. 2020; 60:477-502.

biotics, synbiotics and postbiotics.                  more than 90% of the body’s se­
These substances can be delivered                     rotonin is synthesized in the gut,
through supplements, functional                       Lynch showed the important contri­
foods, and improvements to die­                       bution of indigenous spore-forming
tary intake. For instance, targeting                  bacteria dominated by Clostridia­
the gut microbiome by using dieta­                    ceae and Turicibacteraceae from
ry prebiotics can reverse neuroim­                    the mouse and human microbiota in
mune alterations in middle-aged                       promoting serotonin synthesis. This
mice. In addition, the consump­                       implies that serotonin of microbial
tion of probiotic Bifidobacterium                     origin can have an impact on host
longum 1714 has been associated                       functions, including gastrointesti­
with reduced stress and improved                      nal motility and platelet function.
memory in healthy adults. Current                     In the opposite way, specific domi­
unknowns include dose responses                       nant members of the gut microbio­
and the long-term effects of psy­                     ta are well equipped to respond to
chobiotics’ anxiolytic and antide­                    intestinal serotonin, with an impact
pressant effects.                                     on host lipid metabolism that is not
                                                      completely understood. These re­
Serotonin acts as a node                              sults reveal that certain gut bacteria
                                                      modulate host physiology and its
for gut microbiota-brain                              regulation could have therapeutic
interactions                                          implications n

When going deeper into the com­
munication across the micro­
biome-gut-brain axis, there is also
evidence to suggest that seroto­
nin may be an important mediator.
Jonathan B. Lynch from the Uni­
versity of California, Los Angeles
updated how the gut microbiota
influences body functions by mo­
dulating serotonin levels. Although

                                                                                                        Report 2020 - 14
GUT MICROBIOME DATA WILL HELP CLINICIANS MOVE
TOWARDS CUSTOMIZED PATIENT
HEALTH MANAGEMENT

Joël Doré from the French National      riencing complications associated
Research Institute for Agriculture,     with liver cirrhosis. This means that
Food and Environment discussed          nutritionists or clinicians can have
the progress toward clinical insights   an idea of healthy individuals or pa­
from gut microbiome data. Al­           tients’ lower or higher risk of me­
though it is known that a disrupted     tabolic conditions or response to
host-microbe symbiosis is a com­        certain treatments based on their       “Gut microbiota
mon thread in chronic conditions,       gut microbiota richness assessed        richness might help
Doré acknowledged that harnes­          using full shotgun metagenomic
                                                                                clinicians make
sing available gut microbiome da­       sequencing.
tasets to develop diagnostic, pre­                                              better decisions in
ventive and therapeutic tools is        For gut microbiome data to be­          terms of clinically
not straightforward. In this regard,    come useful in the clinical setting,    managing
a good starting point is grouping       however, it is important to stan­
people according to low or high         dardize sample collection and ana­      the patient.”
richness enterotypes depending          lysis. Only with well documented        Joël Doré
on species diversity/gene count in      microbiome standards that allow
their gut microbiota. While a gut       for robust and reproducible ana­
microbiota showing high richness        lysis will reliable data that provide
is considered a marker of health,       a clear picture of the microbiome
people with low gut microbiota          help guide clinical decisions. In
richness appear to be at higher risk    this regard, the International Hu­
of metabolic conditions such as dia­    man Microbiome Standards project
betes and obesity, may show a re­       has developed standard operating
duced response to treatment (e.g.,      procedures to optimize data qua­
dietary intervention in obesity), and   lity and comparability in the human     “A gut microbiota
may even be more prone to expe­         microbiome n
                                                                                showing high
                                                                                richness is
                                                                                considered a marker
                                                                                of health, people with
                                                                                low gut microbiota
                                                                                richness appear
                                                                                to be at higher risk
                                                                                of metabolic
                                                                                conditions such
                                                                                as diabetes
                                                                                and obesity.”

                                                                                            Report 2020 - 15
Conclusion
                9th edition - 2020

      W      While initial studies in the human microbiome field fo-
             cused on describing alterations in gut microbial commu-
      nities in disease states compared with healthy individuals, du-
      ring the last decade we have gained insights regarding how the
      microbiome shapes health and disease across lifespan. This has
      led to the development of gut microbiome-targeted strategies
      that will allow clinicians to make better decisions in terms of
      clinically managing the patient. Scientists agree that the recipe
      for achieving a healthier gut microbiome that can aid gut-re-
      lated conditions and systemic indications include nutrition,
      prebiotics, probiotics and fermented foods.

      Plenary sessions replay available here.

                                          Tweet Activity of #GMFH2020
                                  1000
    Gut Summit 2020
  was accompanied by              750

interactive conversations
                                  500
 on Twitter. We thank the
  580 participants                250
who played an active role
                                      0
         in the                                 4        5   6   7   8   8     10
                                                                                    March 2020

    #GMFH2020
     conversation.
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                                                                                    Report 2020 - 16
KEY DEFINITIONS
Amylase trypsin inhibitors (ATIs): non-gluten proteins pre­         in the blood, it is a sign of gut barrier impairment, with
  sent in wheat that may promote intestinal inflammation,           subsequent long-lasting effects that go beyond the gut
  increased intestinal permeability and gut dysmotility.            (e.g., obesity has been linked to an increased intestinal
  Research in mice has shown Lactobacillus can degrade              permeability, favoring the shift of LPS from the gut lu­
  wheat ATIs to reduce intestinal dysfunction induced by            men to the bloodstream).
  immunogenic wheat proteins.
                                                                 Microbiome: this term is used for two concepts. One to
Dysbiosis: an imprecise term used for defining a perturbed         refer to the collective genomes harbored by microbes,
  microbial ecosystem compared with the healthy state              and another for referring to the entire habitat, including
  or homeostasis. Instead of being measured by species             the microorganisms and their genomes. Nowadays, this
  richness or diversity, scientists highlight that functional      term is commonly used to refer to the microorganisms
  diversity, stability and resilience also matter when asses­      themselves.
  sing the health of the microbiota and the host. Instead of
  dysbiosis, scientists acknowledge that the terms “diffe­       Microbiota: the community of micro-organisms living in a
  rent”, “altered” or “adapted” are more accurate when re­         specific environment. For example, ‘the gut microbiota’
  ferring to a dysbiotic gut microbiota composition and/           refers to all microbial communities within the intestinal
  or function.                                                     tract.

Enterotype: name for a type of microbiome classification         Microbiota-gut-brain axis: a network comprising the gas­
  described in 2012 based on the proportions of certain            trointestinal tract, the gut microbiota, the enteric ner­
  microbes, in particular Bacteroides, Prevotella, and Ru­         vous system and the brain. Bidirectional communications
  minococcus. As communities of gut bacteria may form a            between the gut and the brain regulate important func­
  spectrum rather than falling into distinct groups, a new         tions, including immunity, digestion, metabolism, satiety
  definition classifies gut microbiota enterotypes into two        and stress reactions.
  entities based on species diversity/gene count. One of
  the enterotypes is low richness (more prevalent in pa­         Operational taxonomic units (OTUs) or phylotypes: similar
  tients with more severe conditions) and the other is high        bacterial individuals based on a predetermined similarity
  richness (considered a marker of health).                        threshold (e.g., 97% similarity).

Fermented foods: foods or beverages whose production             Postbiotics: bacterial metabolites with a direct effect on
  involves extensive microbial growth. The fermented               host nutrition, metabolism and immunity (e.g., short-
  foods containing live organisms that have been charac­           chain fatty acids).
  terized and have clinical evidence of a health benefit are
  considered probiotics. For example, many fermented             Prebiotics: these are substrates that are selectively utilized
  milks have probiotic activity for conditions relating to the      by host microorganisms conferring health benefits. Not
  digestive tract and the immune system.                            all food fibers are considered prebiotics as selective uti­
                                                                    lization by gut bacteria is a requirement for a prebiotic.
Full shotgun metagenomic sequencing: a bioinformatics
  technique that identifies which microbes are present in        Probiotics: live microorganisms that, when administered in
  a sample and their functional potential. It gives more            adequate amounts, confer a health benefit to the host.
  reliable functional predictions compared with 16S rRNA
  sequencing.                                                    Psychobiotics: targeted interventions of the microbiome
                                                                   for mental health benefits. It refers to probiotics, prebio­
Germ-free: a host without a microbiome. Generally refers           tics and other means of influencing the microbiome for
  to mice and rats that were born and reared in a sterile          the benefit of mental health.
  environment for research purposes.
                                                                 Short-chain fatty acids: fatty acids with two to six carbon
Inflammatory bowel disease (IBD): an umbrella term used            atoms that are produced by bacterial fermentation of
   to describe disorders characterized by an excessive             dietary fibers (e.g., acetate, propionate and butyrate).
   swelling of the wall of one section of the digestive tract.
   Types of IBD include Crohn’s disease, ulcerative colitis      Small intestinal bacterial overgrowth (SIBO): a poorly un­
   and pouchitis. Both genetic and environmental factors           derstood entity characterized by an excessive growth of
   potentially affect microbiota composition, which plays a        bacteria within the small intestine. These excessive bac­
   role in IBD pathogenesis.                                       teria have been linked to functional gut disorders such
                                                                   as IBS.
Irritable bowel syndrome (IBS): a common functional di­
    sorder affecting up to 20% of people worldwide, with a       Synbiotics: synergistic combination of prebiotics and pro­
    higher prevalence in women. It is indeed the main moti­        biotics.
    vation behind gastroenterology conditions. Researchers
    believe it may originate from an unbalanced gut micro­       Taxa: a scientifically classified group. Ways of classifying
    biota.                                                         the members of a defined microbiome, in decreasing
                                                                   order: Phylum -> Class -> Order -> Family -> Genus ->
Lipopolysaccharide (LPS): the major component of the ou­           Species -> Strain.
   ter membrane of Gram-negative bacteria. When found

                                                                                                                 Report 2020 - 17
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