Cross-feeding: how many bacteria break down a fibre together

Healthy state

A fibre is rarely a simple chain. A plant cell wall is a meshwork of cellulose, hemicelluloses such as xylan, and pectins, with side chains, branches and many different bonds between the sugar units. Each type of bond needs a matching enzyme. In the small intestine, humans can split almost only starch and simple sugars; gut bacteria take care of the rest. They divide the work into stages: primary degraders break open the large chains, secondary users ferment the fragments into acetate, lactate, succinate and hydrogen, and end users turn these into butyrate Butyrate A short-chain fatty acid and the main energy source for the cells of the colon wall. It strengthens the barrier and dampens inflammation. More in the chapter “Butyrate and other short-chain fatty acids”, propionate or methane. This passing-on is called cross-feeding. Which keystone species sit where, and how to feed them, is covered in the chapter on keystone bacteria.

Many Bacteroides carry their own toolkit for each type of fibre in their genome, a so-called polysaccharide utilisation locus. It includes a sensor that recognises the food, binding proteins and enzymes on the cell surface, and a gate through which the fragments get inside. The kit is switched on when the matching food arrives. Which kits a species has decides what it can eat: for fructans, closely related Bacteroides species differed in exactly this, and in mice it predicted which species won out on a fructan-rich diet.

How far a single bacterium can get is shown by rhamnogalacturonan-II, a pectin component of plant cell walls and the most complex carbohydrate known. It contains 21 different bonds. Bacteroides thetaiotaomicron cleaves 20 of them on its own, using enzyme families that were previously unknown, in a coordinated order, because some bonds only become accessible once side chains are removed. Other fibres need specialists that not everyone has: in a French study, bacteria that break down crystalline cellulose were found mainly in people who produce methane; in the others, Bacteroidetes took over the breakdown of spinach cell walls. Ruminococcus bromii, in turn, has specialised in starch: 15 of its 21 cleaving enzymes belong to a single starch family, and it arranges them into complexes on its surface, called amylosomes.

Breaking down fibre leaves something for others, and often this is no accident. In Bacteroides, some enzymes work outside the cell or are shipped out in small membrane vesicles. The fragments released feed species that could not use the whole fibre on their own. Bacteroides ovatus even breaks down inulin outside the cell at its own cost and thereby feeds Bacteroides vulgatus; in mice this paid off for it, because it received benefits in return. With xylan from cereals, Roseburia intestinalis and Bacteroides share the food because they prefer fragments of different sizes: Roseburia preferably takes up pieces of four to five units. And Bifidobacterium bifidum breaks down breast-milk sugars in a way that lets other bifidobacteria eat along.

The second level of cross-feeding is the waste of fermentation. Faecalibacterium and Roseburia take up acetate released by others while making butyrate. Anaerobutyricum hallii uses lactate and also converts 1,2-propanediol, a breakdown product of certain sugars, into propionate; for this it makes its own vitamin B12, and it was found in the stool of three quarters of the adults studied. Hydrogen, which is produced in almost every fermentation, is taken up by three groups: sulphate reducers turn it into hydrogen sulphide, methane-producing archaea into methane and acetogenic bacteria into acetate. All three occur side by side in the human gut.

The mucus of the gut wall is shared too. Akkermansia muciniphila Akkermansia A gut bacterium that lives on the mucus of the gut wall and stimulates its renewal. In studies, high levels often go along with good metabolic health. More in the chapter “The mucus layer and additives” breaks down the sugar chains of the mucus and releases sugars and acetate. In mixed cultures, Faecalibacterium, Anaerostipes and Anaerobutyricum hallii, which cannot break down mucus themselves, grew on these and made butyrate. In return, A. hallii supplied a form of vitamin B12 with which Akkermansia could make propionate. In this way butyrate can be made right at the gut wall even when no fibre is arriving; so far this has only been shown in the lab.

Disrupted state: causes and effects

If a link in the chain fails, intermediate products are left over. In a healthy colon lactate stays low, because lactate users convert it into butyrate and propionate. In inflammatory bowel disease Inflammatory bowel disease Umbrella term for Crohn’s disease and ulcerative colitis: long-term, relapsing inflammation of the gut that needs medical treatment. More in the chapter “Immune system and inflammation”, by contrast, it can build up strongly. In a lab model of the human gut flora Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity”, added lactate piled up especially at an acidic pH of 5.5, butyrate and propionate fell, and the composition shifted. Communities with few lactate users were less stable from the outset.

Whoever takes up the hydrogen decides the gas. If methane producers or sulphate reducers dominate, more methane or hydrogen sulphide is made instead of acetate. Both are increasingly linked to irritable bowel syndrome Irritable bowel syndrome Recurring abdominal pain linked to bowel movements, without tests finding another cause. Today it is understood as a disorder of gut–brain interaction. More in the chapter “The gut-brain axis”, and methane on a breath test Breath test After drinking a sugar solution, hydrogen and methane in the breath are measured several times. This can reveal sugar intolerances and signs of bacterial overgrowth. More in the chapter “Gut tests: what they show and what they do not” is more often linked to constipation. What determines the balance between the three hydrogen users is not yet clear. More in the chapter on hydrogen sulphide and methane.

Sharing can be exploited. In the lab, species that only grab fragments sometimes grew faster than the primary degraders doing the work. Some primary degraders therefore share little: with yeast mannan, the cell-wall sugar of baker's and brewer's yeast, Bacteroides thetaiotaomicron works in a decidedly selfish way. It makes only rough cuts at the surface and pulls the large pieces inside, so that hardly anything is left for others. Whether a fibre feeds many species or few therefore also depends on who gets to it first.

If the specialist is missing, the fibre is left over. Without Ruminococcus bromii, resistant starch is hardly fermented, and crystalline cellulose can only be broken down by a few species that not everyone carries. Species can be lost over generations on a low-fibre diet. If you barely respond to a fibre, your chain may be missing a link; so far this cannot be determined reliably.

An honest limitation: almost everything in this chapter comes from pure cultures, mixed cultures of a few species, lab models and germ-free mice. How these networks actually run in the human colon with hundreds of species is largely unmeasured, and no stool test can show it today. The principle is established, not the details for any particular person.