Increasing evidence is showing that the gut microbiota can alter the brain and behavior, and thus may play a role in the development of psychiatric and neurodevelopmental disorders, such as autism and schizophrenia.

Animal models are a useful tool to study this mechanism. For example, germ-free (GF) mice, which have never been exposed to microorganisms, are compared with mice exposed to microorganisms, known as conventional colonized mice (CC). Recent studies have schizophrenia and autismreported that GF animals show increased response to stress, as well as reduced anxiety and memory. In most cases, these alterations are restricted to males, in which there are higher incidence rates of neurodevelopmental disorders compared with females.

Mice, like humans, are a social species and are used to study social behavior. A recent study compared GF and CC mice using different sociability tests. GF mice showed impairments in social behavior compared with CC mice, particularly in males. Interestingly, they demonstrate that social deficits can be reversed by bacterial colonization of  the GF gut (GFC), achieving normal social behavior.

Microbiota seem to be crucial for social behaviors, including social motivation and preference for social novelty. Microbiota also regulate repetitive behaviors, characteristic of several disorders such as autism and schizophrenia.

Bacterial colonization can change brain function and behavior, suggesting that microbial-based interventions in later life could improve social impairments and be a useful tool to effect the symptoms of these disorders.

This blog was co-authored by Noèlia Fernàndez and Judit Cabana

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‘If two people eat the same, do they also have the same poop?’

Our microbiologist, dr. Clara Belzer answered this question from Noa (age 12) on Dutch national radio and explained her research on gut-microbes and health.

“Well the answer is yes and no”, starts Clara Belzer. So it’s a great question!

Yes: feces gets to be more similar (both in looks and in smell) if you eat similar things. For instance, eating corn or red beets gives a distinct colour to poop, and eating eggs a distinct smell. So what you eat directly influences your feces.

At the same time, everyone’s excrements are unique. This is due to the unique assembly of bacteria that live in your gut. When you’re born, the first bacteria colonize your gut. During the rest of your life, this colony of bacteria and other microbes keeps developing; growing and changing in response to your diet, illnesses, stress, antibiotic treatments and other influences. The bacteria in your gut help with the digestion of the food you eat. By breaking down the food molecules they can convert these to vital substances such as vitamins and energy. The substances that are not digested, or are left over, leave the body as poop. So because every individual has a unique composition of gut-bacteria, everyone’s poop is unique.

Interestingly, genetics also influence the composition of gut-bacteria. Therefore, the feces of family members is more similar than that of non-family members, and even twins have more similar poop compared to other siblings.

But diet has the biggest influence on your gut-bacteria. If you eat healthy, your bacteria can function well and produce essential substances and energy. If you eat unhealthily, this can disturb the functioning of your gut-bacteria, and this may even contribute to developing for instance diabetes or obesity. Clara Belzer tells that we can even see from someone’s feces if this person has diabetes, or an infection in the intestines.

So studying someone’s poop can tell if the person is healthy or unhealthy. In Clara Belzer’s research she analyzes the gut-bacteria of an individual, to explore if in the future we can give advice to this person on how to adapt his or her diet to improve the assembly and functioning of the gut-bacteria. “For instance, if we can’t find certain important bacteria in someone’s feces, we want to be able to advise this person to eat whole-wheat bread. Then hopefully this stimulates the growth of this specific bacteria and makes the person feel healthier and have a better stool”, she explains.

Clara Belzer is also using mouse models to study a special bacteria, called Akkermansia muciniphila, that in the future may help in treating diabetes and losing weight. She hopes that within the next ten years this will appear as a substance that you can buy in supermarkets in order to improve your health.

You can listen to the interview (in Dutch) here: https://www.nporadio1.nl/wetenschap-techniek/13810-hebben-mensen-die-hetzelfde-eten-ook-dezelfde-poep?fbclid=IwAR1Ihrnmqcq-APOqWGIyvnBTC0ST-KGnhVeRFF2zO0epT0eGuLvbzykc1Eo

Article written by By Clara Belzer, PhD, and Jeanette Mostert, PhD.

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Real time measurements of intestinal
gases: a novel method to study how food is being digested

Researchers in Wageningen (The
Netherlands), have been able to identify for the first time, how gut microorganisms
process different types of carbohydrates by measuring in real time the intestinal
gases of mice. This is not only a novel method to understand how food is
digested but could also tell us more about the role of gut microorganisms in
gut health.

Intestinal gases

The intestinal microbiota is a diverse and
dynamic community of microorganisms which regulate our health status. The
advancement of biomolecular techniques and bioinformatics nowadays allows
researchers to explore the residents of our intestines, revealing what type of microorganisms
are there. However, studying only the microbial composition of an individual
provides limited insights on the mechanisms by which microorganisms can
interact with the rest of our body. For example, far less is understood about
the contribution of the gut microorganisms in the production of intestinal
gases such as hydrogen, methane and carbon dioxide through the breakdown of
food and how these gases affect the biochemical pathways of our bodies.

Intestinal gases consist mostly of
nitrogen, and carbon dioxide, which originate primarily from inhaled air. Hydrogen
and methane though, are produced as by-products of carbohydrate fermentation
(break down), by intestinal microorganisms. However, not all carbohydrates are
digested in the same way. For instance, food with simple sugars can be rapidly absorbed
in the small intestine unlike complex carbohydrates such as fibers, which reach
the colon where they are digested by the colonic microbiota.

Lower_digestive_system

Measuring hydrogen in mouse intestines

To study these interactions and gain
knowledge on how microorganisms process carbohydrates, the research team led by Evert van
Schothorst from the Human and Animal Physiology Group of Wageningen University
(WU) in collaboration with the WU-Laboratory of Microbiology fed mice two
different diets with the same nutritional values but with different types of carbohydrates
(1). The first diet contained amylopectin,
a carbohydrate which can be digested readily in the small intestine while the
second diet contained amylose, a slowly digestible carbohydrate that is
digested by intestinal microorganisms in the colon.

Animals fed the easily digestible carbohydrates
showed minimal production of hydrogen whereas the group fed with the complex
carbohydrates presented high levels of hydrogen. Moreover, the two groups were
characterized not only by distinct microbial composition (different types of
bacteria present) but also distinct metabolic profiles (short chain fatty acids),
suggesting that the type of carbohydrate strongly affects microbial composition
and function.

The importance of
hydrogen

Hydrogen consumption is essential in any anoxic
(without oxygen) microbial environment to maintain fermentative processes. In
the intestine it can be utilised through three major pathways for the
production of acetate, methane and hydrogen sulphide. These molecules are
critical mediators of gut homeostasis, as acetate is the most predominant short
chain fatty acid produced in mammals with evidence suggesting a role in inflammation and obesity (2). Methane, which is produced by a specific type of microorganisms,
called archaea, has been associated with constipation related diseases, such as
irritable bowel syndrome(3) and also recently with athletes’ performance (4)! Finally hydrogen sulphide
is considered to be a toxic gas, although recent findings support the notion
that it also has neuroprotective effects in neurodegenerative disorders such as
Parkinson and Alzheimer diseases (5).

To the best of our knowledge, this is the first time that food-microbiota interactions have been studied continuously, non-invasively and in real time in a mouse model. Hydrogen is a critical molecule for intestinal health and understanding its dynamics can provide valuable information about intestinal function, and deviations in conditions such as Crohn’s disease or irritable bowel syndrome (IBS).

Further reading

1. Fernández-Calleja, J.M., et al., Non-invasive continuous real-time in vivo analysis of microbial
hydrogen production shows adaptation to fermentable carbohydrates in mice.

Scientific reports, 2018. 8(1): p.
15351.

https://www.nature.com/articles/s41598-018-33619-0

2.
Perry, R.J., et al., Acetate mediates a
microbiome–brain–β-cell axis to promote metabolic syndrome.
Nature, 2016. 534(7606): p. 213

3. Triantafyllou, K., C. Chang, and M. Pimentel,
Methanogens, methane and gastrointestinal
motility.
Journal of neurogastroenterology and motility, 2014. 20(1): p. 31.

4. Petersen, L.M., et al., Community characteristics of the gut microbiomes of competitive
cyclists.
Microbiome, 2017. 5(1):
p. 98.

5. Cakmak,
Y.O., Provotella‐derived hydrogen sulfide, constipation,
and neuroprotection in Parkinson’s disease. Movement Disorders, 2015. 30(8): p.
1151-1151.

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In my previous blogs, I explained the research questions of my study. This study will be performed in two cohorts which I will elaborate on in this current blog about early life nutrition and studying gut microbiota. The cohorts are called BIBO and BINGO.  

BIBO stands for ‘Basale Invloeden op de Baby’s Ontwikkeling’ (in English: basal influences on  infant’s development). Recruitment of this cohort started in 2006, and a total of 193 mothers and their infants were included. At age 10, 168 mothers and their children still joined the BIBO study; the attrition rate is thus low. The majority of the mothers are highly educated (76%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. A unique aspect of the BIBO study is the number of stool samples collected in early life. Also, detailed information about early life nutrition has been recorded during the first six months of life (e.g. information on daily frequency of breastfeeding, formula feeding, and mixed feeding). Together, these stool samples and nutrition diaries provide important insights in the relations between early life nutrition and gut microbiota development. Data about children within the BIBO cohort will be collected at age 12,5 years and 14 years. At 12,5 years, the participants will be invited to the university for an fMRI scan (more information about the fMRI scan will be given in a future blog). At age 14, children’s impulsive behavior will be assessed by means of behavioral tests and (self- and mother-report) questionnaires.

BINGO stands for ‘Biologische INvloeden op baby’s Gezondheid en Ontwikkeling’ (in English: biological influences on infant’s health and development). When investigating biological influences on infant’s health and development, it is important to start before birth. Therefore, 86 healthy women were recruited during pregnancy. Recruitment took place in 2014 and 2015. One unique property of the BINGO cohort is the fact that not only mothers were recruited, but also their partners. The role of fathers is often neglected in research, and thus an important strength of this BINGO cohort. Another unique property is that samples of mothers’ milk were collected three times during the first three months of life, to investigate breast milk composition. As for many infants their diet early in life primarily consists of breast milk, it is interesting to relate breast milk composition to later gut microbiota composition and development. Currently, 79 mothers and children, and 54 fathers are still joining the BINGO study. The average age of the participants at the time of recruitment was 32 years for mothers and 33 years for the father. Majority of the parents within this cohort are highly educated (77%) and from Dutch origin (89%). The number of boys (52%) and girls (48%) in this cohort are roughly equally divided. At age 3, children’s impulsive behavior will be assessed by means of behavioral tests and mother-report questionnaires.

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