Gas Biology Research in Clinical Practice. Группа авторов

      Stomach and Duodenum

      Since the esophagus enters the posterosuperior aspect of the stomach, gas is trapped above liquid overlying the gastroesophageal junction in the supine position. Therefore, most swallowed air is entrapped in the stomach and can travel along the small bowel.

In the upper gut, large quantities of gas are physiologically generated from chemical reactions of hydrogen ion and bicarbonate. For 1 mEq H⁺ neutralized by bicarbonate in pancreatic, biliary, or duodenal secretions, 22.4 ml CO₂ is produced [3]. Fat digestion causes much gastric acid secretion and would result in an estimated CO₂ production rate of 1,400 ml/h. Most CO₂ produced during normal digestion is absorbed along the small bowel [4]. Thus, the luminal gas in the upper digestive tract is partly swallowed and in part originates from a series of chemical reactions of the foodstuffs within the gut. Theoretically, the calculated amount of CO₂ produced in the upper gut is 33.6 liters per day (1,400 ml multiplied by 24 h). However, the actual volume of CO₂ liberated as gas may be far below this value owing to the slow decomposition of H₂CO₃ to CO₂ and H₂O in the absence of carbonic anhydrase and the relatively high solubility of CO₂ in water [5]. Presumably, approximately 5-10 liters of CO₂ seems to be produced and released into the lumen by chemical reactions.

As mentioned above, the pCO₂ rises dramatically in the duodenum, resulting in diffusion of CO₂ from lumen to blood, whereas CO₂ in swallowed air diffuses from the blood into the stomach [6]. Because the pO₂ of swallowed air is greater than that of blood in the stomach, O₂ is absorbed from the stomach. The pN₂ of swallowed air is slightly higher than that of venous blood in the stomach, possibly resulting in very slow absorption. In the duodenum, N₂ diffuses from blood into the lumen according to the partial pressure gradient because of the down gradient established by CO₂ production. In contrast, since pH₂ and pCH₄ are always higher in the lumen than in the blood, gases are constantly diffusing from lumen to blood. In our previous study using endoscopy, H₂ and CH₄ gases are more frequently detected in the stomach than expected, regardless of the presence of abdominal symptoms [7] although it has been reported that the stomach and duodenum harbor very low numbers of microorganisms adhering to the mucosal surface, typically less than 10³ bacteria cells per gram of counts [8]. Fried et al. [9] reported that most of the bacteria identified from the duodenal aspirates belonged to species colonizing the oral cavity and pharynx, suggesting a descending route of colonization. Also, Thompson et al. [10] indicated that fermentation of ingested carbohydrate by oropharyngeal bacteria could contribute to measured breath hydrogen values soon after meal ingestion. Moreover, intraduodenal H₂ levels were higher in patients with severe atrophic gastritis than those without atrophic gastritis, and there was a progressive increase with the progression of atrophic gastritis [11]. In contrast, the intragastric H₂ level was the highest in patients with gastric mucosa of the closed type and was significantly higher than in those with severe atrophic gastritis. These results suggest that extensive atrophic gastritis may be more closely related to bacterial overgrowth in the jejunum, compared to that in the stomach.

      Small and Large Intestine

There is a progressive increase in numbers of bacteria along the jejunum and ileum, from approximately 10⁴ in the jejunum to 10⁷ colony-forming units per gram of contents at the ileal end, with a predominance of Gram-negative aerobes and some obligate anaerobes [8]. In contrast, the large intestine is heavily populated by anaerobes and bacteria counts reach densities around 10¹² colony-forming units per gram of luminal contents because transit time is slow and microorganisms have the opportunity to proliferate by fermenting available substrates derived from either the diet or endogenous secretions. Because bacteria represent the sole source of gut H₂ and CH₄, fasting breath H₂ and CH₄ gases have been used as markers of colonic fermentation [12, 13]. As H₂ production increases when a small amount of carbohydrate is supplied to colonic bacteria, the measurement of breath H₂ concentration has been proposed as an indicator of carbohydrate malabsorption [14]. H₂ gas is produced at a rate of 4 liters for every 12.5 g of undigested carbohydrate. Since it has been reported that 2-20% of carbohydrates escape small intestinal absorption [16] and men in their 40s consume 428 ± 72 g of carbohydrates [17], the calculated amount of H₂ produced in the colon is 2.7-27 liters/day (428 g × 0.2 × 4 liters/12.5 g = 27.4). Approximately 20% of all H₂ ingested or produced is eliminated via the lungs; the rest is either consumed or expelled via the rectum.

Several mechanisms of H₂ utilization have been reported in the human large intestine including methanogenesis, dissimilating sulfate reduction, and acetogenesis. The latter process corresponds to the reduction of 2 mol of CO₂ by 4 mol of H₂ to form 1 mol of acetate [18]. This process greatly decreases colonic gas volume. Methanobrevibacter smithii, which uses H₂ to reduce CO₂ to CH₄, is responsible for almost all the CH₄ produced in the intestine [19]. Since CH₄ production occurs primarily in the left colon whereas H₂ is produced primarily in the right colon [20], H₂ produced in the left colon may be rapidly converted to CH₄. CH₄ appears in the breath only when the numbers of methanogenic bacteria reach a critical level, about 10⁸/g dry weight counts [19].

      Clinical Problems

      Irritable Bowel Syndrome

Intestinal gas is often incriminated as a major cause of irritable bowel syndrome (IBS), particularly when bloating is predominant, but no general relationship between intestinal gas and IBS symptoms has yet been established. Koide et al. [21] found a significantly increased intestinal gas volume score in plain abdominal radiographs in patients with IBS as compared with healthy controls, suggesting that abnormal accumulation of intestinal gas could be a problem in these patients. In contrast, Morken et al. [22] reported that intestinal gas volume is not correlated with abdominal discomfort after lactulose challenge and concluded that intestinal gas may not be the major cause of abdominal discomfort following carbohydrate ingestion in IBS.

In some diseases that favor bacterial proliferation, such as inflammatory bowel diseases, it may be difficult to determine the extent to which clinical deterioration is caused by bacterial overgrowth or the primary intestinal diseases. Actually, many individuals harbor bacterial overgrowth without symptoms. Thus, the clinical features of bacterial overgrowth,